Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
IntechOpen is proud to announce that 179 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\n
Throughout the years, the list has named a total of 252 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
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1. Introduction
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With the intense contest for ground-level space within high-density urban districts, urban agriculture has taken on multiple forms and occurs in different locations, such as peri-urban farming, urban soil-based farming, indoor farming and rooftop farming [1]. Urban agriculture was initially conceptualized as a response to increasing concerns for food security within the city, with the focus on the potential for mass production within a localized food system that includes production, processing, distribution, consumption and recycling [2]. More than 30% of the food requirements of the City of Oakland are planned to be provided from within the physical limits of the city through city council’s sustainable food system [3]. However, within the complex morphology of high-density cities, the contest for space and strict land use and building controls, the large-scale contiguous spaces required for economic mass agricultural production are seldom available. Many micro-farming enterprises, however, have emerged in cities around the world as community gardens and allotment gardens [4]. Occupying small-scale, marginalized and fragmented “leftover” spaces, these occur on sites of uncertain ownership and ambiguous regulatory control.
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A clear expression of this phenomenon is the spontaneous appearance in the last decade of more than 60 rooftop farms on underutilized flat roof spaces across the dense urban districts of Hong Kong [5]. These urban rooftop farms are composed of numerous lightweight surficial planter boxes (as opposed to the built-in planting constructions typical of green roofs) which are individually rented to the general public through community enterprise organizations or provided to relevant groups by corporate or institutional owners. Proximity to the people’s living and working spaces have made urban rooftop farms popular, with all farms reporting that they are constantly heavily oversubscribed. Farm owners have suggested that the strong demand for participation is motivated by the opportunities it provides for social interaction, passive recreation, health, education and self-achievement. This contrasts with the HKSAR Government’s recent policy initiatives for urban agriculture which are focused on economic and productive values [6]. In consequence, urban rooftop farms in Hong Kong are in an ambiguous situation between formal centralized city planning and informal community enterprise action. To understand the social benefits of rooftop farming within an urban context of contested space and extreme land value, this study looked to monetize social value through cost-benefit analysis and willingness among participants to pay for extra social benefits derived from the practice.
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1.1 Social value of urban rooftop farming
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Social value has long been a consideration within environmental justice discourses; however there has been relatively little research on the social values of urban agriculture and almost none on urban rooftop farming [7]. As with urban agriculture, the few policy debates that have occurred on urban rooftop farming have focused on the potential economic value—the monetary profits that might be generated by selling food produced within the city and generalized concerns for global food security. Around the world, however, very few large-scale commercial urban rooftop farms have been successfully established, and these have only been achieved by retrofitting rooftops with large-scale greenhouses, e.g., AeroFarms in the USA [8] and urban farmers in the Netherlands [9]. The large majority of urban rooftop farms have been small-scale social and community enterprises. In recent years, discussion about the practice has migrated onto to potential contribution to urban environment and greening [1, 10, 11, 12, 13]. Urban rooftop farms have been suggested as possible patches that might visually and ecologically link existing green spaces and corridors within an integrated green infrastructure system and help mitigate urban heat island effects [14]. It has been shown that urban rooftop farms support far higher biodiversity (some have upwards of 200 plants species) than green roofs [15].
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Only recently have discussions of the social values of urban rooftop farming begun to appear in the literature. Although social values are considered an important principle within broader concepts of urban sustainability, their recognition and development are lagging [16]. This is commonly attributed to the fact that social values associated with the external environment, such as green spaces and allotment gardens, are intangible and difficult to measure [17]. Social value is usually assumed to be generated through communal physical activity within a space, for example, social groups collaborating on planting activities [18]. Long return on investment makes social value hard to calculate and difficult to monetarize, metrics that are commonly required for inclusion in policy decision-making [19].
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Through a review of international case studies, social values of urban rooftop farming were initially investigated from three aspects: social capital theory, landscape projects and urban agriculture practices and with the aim of building a systematic framework of social values for urban rooftop farming. As Dika and Singh [20] noted, the decomposition of a broad concept into factors and indicators can improve understanding and help the policy adaptation in specific contexts.
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Ideas of social values are based on social capital theory which focuses on balancing different social groups by creating a sense of fairness from collaboration [21]. Social group integration and empowerment are key factors discussed by scholars. Dubos [22] suggests that social capital should be considered in two forms: structural network and cognitive value. Doherty further explains that the structural network in an inclusive society should cross generations and identities and consist of the behaviour-related indices of trust, informal networking, mutual support, reciprocity and solidarity [23, 24]. At the same time, cognitive value is a significant assessment for empowered citizens which is usually obtained from increasing self-satisfaction, achievement and leadership in the society [25, 26].
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As an emergent landscape typology, performance measures for urban rooftop farming have yet to be developed [27]. Methods of measuring performance of built landscape have tended to assess physical objects and functional efficiency [28, 29]. Of the few approaches that have evaluated changes in social aspects, Landscape Performance Series (LPS) and Case Study Investigation (CSI) contain the most instructive framework, as they categorize recreation, health, education and food production as core social value factors that enhance sustainability in landscape projects [27].
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In the absence of previous research on the specific social values of urban rooftop farms, this research drew upon discussions of social values related to urban agriculture in general. This allowed indicators for an urban rooftop farming social values framework to be identified. The urban agriculture matrices framework developed by Design Trust for Public Space program in New York highlighted the significant benefits through increased physical health and social empowerment from growing vegetables [30]. Specifically, physical, mental and dietary health can be summarized from the research outcome. Social empowerment has been further supported via environmental and food education, leadership and socializing activities which are increasingly important by-products of all forms of urban agriculture. Other researchers have identified unique collective social welfare being generated through urban rooftop farming [7, 31, 32]. Tian and Jim addressed the social value of additional open spaces to the surrounding communities through multifunctional roof spaces, noting that given the limited land in highly dense cities, retrofitting urban farms to rooftops can effectively activate large numbers of vacant spaces within the city for social benefits [32]. Prior research studies have also indicated that dynamic factors are involved in the generation of social values through the practice of urban agriculture.
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1.2 Framework of social benefits of urban rooftop farming
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Based on these interdisciplinary research studies, a social value framework for urban rooftop farming was developed, specific to the Hong Kong context (Table 1). This allows a spectrum of social benefits of urban rooftop farming to be considered, with respect to the diverse stakeholders’ (state and individual) interests. The framework compares the social values generated by urban agriculture, green roof installations and rooftop farms; identified from published research papers; and categorized under six factors: health, education, community recreation, urban improvement, social empowerment and social group integration. Urban rooftop farming generates the greatest amount of activity across all the different social values.
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URF social value framework
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Urban agriculture
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Green roof
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Rooftop farms
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Category
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Factors
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Social benefits
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√
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√
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Social benefits
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Health
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Improve physical health
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√
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√
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Improve mental health
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√
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√
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Experience health habit and diet
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√
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√
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Education
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Increase environmental awareness
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√
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√
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Promote sustainable living
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√
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√
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Increase organic food knowledge and demand
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√
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√
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Gain practical skills by working in urban rooftop farms
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√
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√
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√
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Community recreation
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Provide extra open space for communities
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√
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√
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√
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Provide visual aesthetic value
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√
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√
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√
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Increase space using comfortableness
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√
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√
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√
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Urban improvement
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Serve as a planning tool to fill vacant spaces in cities
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√
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√
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Extension of the life expectancy of roofs
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√
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Diverse the multifunctions of roof spaces
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√
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√
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Good for urban or building retrofitting
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√
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√
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√
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Social empowerment
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Improve users/residents’ life satisfaction
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√
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√
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Enhance community participation
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√
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√
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Develop leadership
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√
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√
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Provide job opportunity to communities
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√
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√
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Social group integration
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Empower marginalized groups
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√
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√
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Enrich aging life
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√
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√
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Enhance parent and children relationship
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√
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√
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Form social networks
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√
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√
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Create social solidarity among diverse groups
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Table 1.
Social value framework for urban rooftop farming.
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2. Hong Kong urban rooftop farming in a high-density city
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Within HKU’s broad-based “edible roof” initiative which examined the rooftop farming phenomenon across Hong Kong, this specific research study examined eight urban rooftop farms within Hong Kong (including enterprise, social enterprise and individually oriented modes) to determine the nature and scale of the social values that urban rooftop farms could generate.
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Hong Kong is an extreme example of high-rise high-density urban settlement, with severe contest for ground-level space, very high land values and a passive governance structure. Although HKSAR Government’s New Agricultural Policy 2014 and Hong Kong 2030+ strategic planning statement do acknowledge urban rooftop farming practices within the general concept of urban agriculture, intention has focused primarily on economic productivity, and no specific institutional, regulatory or technical support is offered to the small-scale grassroot organizations that practice farming. Despite this, more than 60 urban rooftop farms have spontaneously appeared in the city since 2008 covering some 15,000 sqm of previously underutilized roof space [5]. The majority of the farms are located on industrial or institutional buildings within the older urban districts (Figure 1). Based on a definition of the physical and operational limits of rooftop farming practices and subsequent suitability assessment of all existing buildings in the territory, the potential farmable roof spaces that might exist within the city have been estimated at approx. 595 ha [5]. Although typically small-scale and disparate, these spaces are all in close proximity to large urban populations and collectively offer an expansive opportunity for generating social value (and its attendant economic advantages) if activated for rooftop farming [33].
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Figure 1.
Locations of urban rooftop farms in Hong Kong, as of 2016 (data source: Mathew Pryor ongoing research and Google earth).
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Physical and operational characteristics of the three modes of urban rooftop farming in Hong Kong were identified through systematic site survey and typological study (Figure 2). Social enterprise farms aim to promote social change through a sustained commercial business [34]. Social enterprises, such as City Farm and Fun n Farm, generate social impacts by renting out the planting plots to the public. Planting plots typically consist of shallow free-standing black plastic crates filled with lightweight soil, with bamboo or plastic pipe frames above supporting screen netting [33, 35]. Crops are selected and taken care of by farmers, although daily watering is undertaken by farm managers. Training courses (for different skill levels) and related social and craft activities are commonly offered. Farmers rent any number of boxes per month, depending on their ambition and commitment. All farms report extensive waiting lists. The depth of soil and exposure to wind limits species choice to some extent, but a wide range of leafy greens, climbing plants, root vegetables and herbs can be grown. Enterprise-oriented farms are operated by private companies and business or large institutions (universities, schools, hospitals) located on their own premises. Access to the farms is restricted to employees or institutional members. They are similar in physical form and nature to social enterprise farms but additionally provide leisure and social space for employees, with tables, chairs, etc. Individual rooftop farms were very small-scale and only found on residential buildings. Their form was typically more complex and less ordered, and both the form of the planter and the crop species were far more diverse. As they depend solely on the individual owner’s willingness and availability, they were seen as being more vulnerable.
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Figure 2.
Typological study of urban rooftop farm in Hong Kong (photo taken by Mathew Pryor and ting Wang).
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3. Research design
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Based on this understanding of the local context, the research study was structured around a participant opinion survey and semi-structured interviews with the operators from five selected farms. The survey aim was to validate the preliminary urban rooftop farming social value framework and to quantify the intangible social values from the perspective of the users, including those with and without experience of farming. Subjects were randomly selected from the five farms and from the surrounding residential communities, respectively. A total of 108 answers were collected.
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Semi-structured interviews were conducted with farm operators from the five farms, in order to understand the monetary influence of social values in urban rooftop farming and to verify the findings from survey. Questions focused on topics such as modes of operation and costs, as well as physical arrangement and planting types. Farm cost data was used in cost-benefit analysis and “willingness to pay” based on contingent valuation methods and perception preference methods. As willingness to pay is influenced by the perceived utility, personal preference of use and socioeconomic environment of the subjects, the survey was designed to obtain the information about various degree of willingness and payments, preference of social values developed in framework and personal socioeconomic information including gender, employment, education and income levels.
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4. Findings
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The majority of respondents (77%) perceived social values to be the most important benefits of urban rooftop farming, compared with environmental values (58%) and economic benefits (10%). Women and the middle-aged (30–50) were found to be the predominant users of urban rooftop farms—by both number and time. This finding was confirmed through farm membership records and observations of farm managers. Meanwhile, the majority of farm participants were from middle- to high-income groups.
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4.1 Social values with a preference for personal socialization
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The perception of social values was complex, with individuals expressing degrees of perception toward the six different factors (Figure 3). However, personal socialization benefits were identified most strongly among the six factors. Health (53%) and education (62%) were the factors most perceived by respondents that directly link to the personal enhancement in social statues. Planning social welfare (40%), social group integration (40%), community recreation (35%) and social empowerment (25%) were of less importance by respondents.
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Figure 3.
Perception distribution.
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Disparity of social benefit preferences reflects the difference between personal experience values and group conceptual values. Personal health and education are the most direct feelings obtained through daily activities; however, individuals perceive larger scale community and collective benefits indirectly. For instance, though social group integration was not perceived as very significant on the whole, the indicators for enriching the life of the aged and enhancing intergenerational relationships were perceived as highly significant because of the close personal feelings attached. “Developing leadership” and “providing job opportunities” were the two least important indicators among the social empowerment factors, in interview participants questioned “how can leadership be improved by just growing vegetables?” To some extent, this makes sense because it is hard for leadership development to be perceived by the users themselves unless there is an external instructor who guides the activity and highlights the purposes behind it. This may necessitate long-term observation of farm participation organized by experienced teams or working feedback from the employment company. At this point, there is no measurable index for conceptual benefits. In addition, the benefits of increased job opportunities for the society will only be realized when urban rooftop farming becomes a city-scale endeavor. Current rooftop farms are individually too small to be measured in the employment indicator.
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4.2 Willingness to pay for social benefits
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Many respondents indicated willingness to pay for the social value experience derived from urban rooftop farming. While some were conservative about payment, “I don’t have extra time to enjoy the rooftop farms” (32%); “I cannot afford to pay or buy the service” (19%), the majority of respondents (87%) were willing to pay. The average payment reported during the survey was HK$ 220 per month/person/half square meter. In comparison with the current charge for renting a plot in an urban rooftop farm (HK$ 190), this suggested an increased perception of social values among users.
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Just asking questions about individual payment decisions encouraged respondents to consider the benefits and the maximization of utility. Willingness to pay was found to be related significantly to the degree of understanding of urban rooftop farming, level of education and income level. Willingness to pay increased with the cognitive level of participants from “no idea” to “have participated in urban rooftop farming.” Practicing farmers were willing to pay more (HK$ 232) than those that had not previously participated (HK$ 194). Most of the respondents who are willing to pay were from higher levels of education (undergraduates and graduates), as well as higher-income groups (Figure 4).
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Figure 4.
Significant factors in willingness to pay.
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4.3 Cost-benefit analysis: The monetary influence of social values
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Apart from the multiple implications of social values in urban rooftop farming, this research also demonstrates the potential monetary influence through the application of cost-benefit analysis in comparing the marginal benefits (social values) with the existing benefits and costs (capital and recurrent). According to [25, 36], the following cost-benefit analysis components can provide an economic spectrum of social values in urban rooftop farming which can influence government decision-making and contribute to social well-being:
Among the financial information obtained from operators, City Farm Kwun Tong was chosen as a prototype for this calculation due to its comprehensive operational mode and representativeness of other farms in Hong Kong. Cost-benefit analysis in the study used the basic scenario of a rooftop farm in Hong Kong. The prices and amounts were all generic estimates in order to provide the minimum costs and benefits.
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First year revenues generated through urban rooftop farming were found to barely offset the costs in Hong Kong. In the prototype case, the gross costs and benefits of urban rooftop farming in the first year were HK$ 730,400 and HK$ 764,760, respectively. In subsequent years, the annual recurrent commercial benefits exceeded the annual recurrent costs HK$ 530,400, giving a benefit-cost ratio of 0.32 (234,360/7,304,000), which suggested a likely payback period of 38 months. This factors in the high initial capital cost to establish a rooftop farm which includes building retrofitting costs and the purchase of equipment. Farm managers reported that the business stabilized after the second year and revenues were expected to increase in a long term.
\n
However, the current amount of payment is based on a narrow view of farming participation (HK$ 190 per month/person/half square meter). As suggested by the willingness to pay analysis, once participants took into account the social values derived from their farming activities, they might be willing to pay more (HK$ 220). If fees were raised to this level, it would significantly alter and increase the gross benefits (to HK$ 872,760 per year) and shorthorn the payback period (to 26 months). The results suggest that cost-benefit analysis provide a useful basis on which to reconceive the financial viability of the urban rooftop farms.
\n
\n
\n
\n
5. Discussion
\n
In Hong Kong, formal green initiatives in the urban area have come a long way from the development of public parks in the 1970s to the promotion of green roof designs through sustainable building directives in the 2000s. However urban rooftop farming has not been formally recognized and exists still within gray areas of urban planning legislation and building control.
\n
As evidenced by these findings, the disparity of multifaceted social values aligns with previous literature on social capital theory. Cognitive values are directly related to the individuals in the society such as the effects of health and education improvement, while structure values are indirectly built through expanding network in society which needs more efforts to achieve. For instance, collective assets like the urban economy prosperity and social solidarity not only improved by mobilizing individuals through urban rooftop farming but also need more complex catalysts.
\n
Different levels of understanding of social values have been identified within previous landscapes value research [37]. Individual perceived values in the landscape, concentrating on health and general wellbeing, have most readily been identified: collective values relating to spatial planning and resource management have been less mentioned by subjects. This disparity is also rooted in the physical nature of existing urban rooftop farming practices. According to observations made during this research, rooftop farming activity is explicitly individual due to space limitations. A large number of planting plots were arranged side by side within physically constrained roof spaces, inhibiting interaction. Participants work by themselves on individual plots while only “keeping an eye” on surrounding plots farmed by others. This mode of operation might explain the higher perception of direct personal health and education benefits. The lack of additional social space in social enterprise farms and the solitary nature of individual farms may reduce perceptions of collective social value such as engagement of the community or improvement of the urban environment.
\n
Previous research has not explored the monetary influence of social benefits, which is required for urban rooftop farming to be incorporated into urban policy-making. For instance, on average the payback period for farms is shorter than for green roofs in Hong Kong (27 months) and for ground-level urban agriculture projects (96 months) [25, 38]. The monetary influence of social values is likely to become amplified as urban density increased. Governments, as well as building owners, are likely to be more willing to invest in urban rooftop farming for both the economic benefit and social value through community sustainability.
\n
\n
\n
6. Conclusion and further research
\n
A shift in the thinking about the products of urban rooftop farming from food security and urban greening to social benefits and positive support to activate urban rooftop spaces would create significant opportunities for aligning individual motivations and state interests, thereby achieving a more sustainable city. Though current urban rooftop farming is undertaken by individuals and grassroots organizations, with limited policy or technical supports from city authorities, users still perceived considerable social benefits in the form of sustainable living, environmental knowledge and enhanced relationships within social groups. Users’ willingness to pay for the experience indicates that urban rooftop farming is a passive social activity which can be enhanced by collaborative activities and by-products of farming which include talking, working side by side, standing and comparing.
\n
The implication of the multifaceted social values of rooftop farming suggests a changing perception of urban agriculture. With the increasing speed of urban densification, urban agriculture, constituted by complex social values and diverse interests from stakeholders, has the capacity to be a public good for cultural exchange and enhancing social coherence. This changing perception suggests the need for greater stakeholder support, recognition in legislation and integration with urban planning and building control processes. As an emerging urban activity, further studies are required. For instance, the higher preference for health and education as social benefits in this research requires more specific study to develop detailed instruments for those single indicators within particular groups. In addition, as this study only addressed the social values of urban rooftop farming in Hong Kong, further studies in different contexts and forms could help to expand the urban agriculture discourse.
\n
\n
Acknowledgments
\n
The authors would like to thank the staffs from City Farm, Rooftop Republic Urban Farming as well as an anonymous friend for their generous assistance in the data collection of this research. This research received publication fund from the University of Hong Kong Department of Architecture.
\n
\n
Appendices
\n
List of semi-structured interview questions:
When was your rooftop farm built?
How was your urban rooftop farm established? What kind of costs is included in the farm? Can you give me the rough number about the cost?
How does your farm operate on a daily basis? How many people did you hired and in what position? What kind of benefits can be earned in the urban rooftop farm? Can you give me the rough number about the benefits?
What are the difficulties you faced when setting up an urban rooftop farm in Hong Kong?
How big is your urban rooftop farm?
What kind of activities you have in your farm?
Can you estimate roughly how many people come to your rooftop farm on a regular basis?
What kind of species can you grow in your rooftop farm?
How do you think about the distribution characteristics of the participants in my questionnaire? Is it consistent with your observation every day?
How do you think about the existing result of questionnaire that shows the low perception of the collective social value in URF? Are you considering to add more public spaces or people to socialize in the future?
\n
\n',keywords:"urban agriculture, rooftop farming, social benefits, sustainability, cost-benefit analysis",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/69221.pdf",chapterXML:"https://mts.intechopen.com/source/xml/69221.xml",downloadPdfUrl:"/chapter/pdf-download/69221",previewPdfUrl:"/chapter/pdf-preview/69221",totalDownloads:472,totalViews:0,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,dateSubmitted:"December 17th 2018",dateReviewed:"August 21st 2019",datePrePublished:"September 24th 2019",datePublished:"October 30th 2019",dateFinished:null,readingETA:"0",abstract:"As cities densify, areas available for agriculture within the city become increasingly small and infeasible for mass production. In parallel, many cities have seen a rapid rise in establishing community-based micro-farming, operating within marginal spaces of uncertain ownership or regulations. Prominently in Hong Kong, more than 60 urban rooftop farms have spontaneously appeared in the last 10 years on buildings. High application rates for renting plots in these informal farms suggest a strong demand in the population. Motivations cited by participants of rooftop farms are typically social, although social values have yet to be specifically defined or objectively measured. Hong Kong Special Administrative Region Government’s new agricultural policy conceives urban agriculture as a commercially productive practice. In consequence, urban rooftop farming lies awkwardly between formal city planning and informal community practices. A study of five rooftop farms in Hong Kong found, through participant opinion surveys and cost-benefit analysis, that the social benefits to participants were multifaceted with a preference on personal socialization and that they were willing to pay for the experience. The results suggest that if the products of rooftop farming could be conceived as being social, rather than food production, individual motivations and state interests could be aligned and the available roof space activated to achieve a more sustainable city.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/69221",risUrl:"/chapter/ris/69221",book:{slug:"agricultural-economics-current-issues"},signatures:"Ting Wang and Mathew Pryor",authors:[{id:"289674",title:"Ph.D. Student",name:"Ting",middleName:null,surname:"Wang",fullName:"Ting Wang",slug:"ting-wang",email:"sarahwin@connect.hku.hk",position:null,institution:null},{id:"289677",title:"Prof.",name:"Mathew",middleName:null,surname:"Pryor",fullName:"Mathew Pryor",slug:"mathew-pryor",email:"matthew.pryor@hku.hk",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1 Social value of urban rooftop farming",level:"2"},{id:"sec_2_2",title:"1.2 Framework of social benefits of urban rooftop farming",level:"2"},{id:"sec_4",title:"2. Hong Kong urban rooftop farming in a high-density city",level:"1"},{id:"sec_5",title:"3. Research design",level:"1"},{id:"sec_6",title:"4. Findings",level:"1"},{id:"sec_6_2",title:"4.1 Social values with a preference for personal socialization",level:"2"},{id:"sec_7_2",title:"4.2 Willingness to pay for social benefits",level:"2"},{id:"sec_8_2",title:"4.3 Cost-benefit analysis: The monetary influence of social values",level:"2"},{id:"sec_10",title:"5. Discussion",level:"1"},{id:"sec_11",title:"6. Conclusion and further research",level:"1"},{id:"sec_12",title:"Acknowledgments",level:"1"},{id:"sec_12",title:"Appendices",level:"1"}],chapterReferences:[{id:"B1",body:'Sanyé-Mengual E et al. Resolving differing stakeholder perceptions of urban rooftop farming in Mediterranean cities: Promoting food production as a driver for innovative forms of urban agriculture. Agriculture and Human Values. 2016;33(1):101-120\n'},{id:"B2",body:'Smit J, Nasr J, Ratta A. Urban Agriculture: Food, Jobs and Sustainable Cities. New York, USA: The Urban Agriculture Network, Inc.; 1996. pp. 35-37\n'},{id:"B3",body:'Green M. Oakland Looks toward Greener Pastures T.O.F.P. Council. Oakland: Edible East Bay; 2007. pp. 36-37\n'},{id:"B4",body:'Van Veenhuizen R. Cities farming for the future. Cities farming for future. In: Urban Agriculture for Green and Productive Cities. The Netherlands: RUAF Foundation, IDRC and IIRP, ETC-Urban agriculture, Leusden; 2006. pp. 2-17\n'},{id:"B5",body:'Hui S. Green roof urban farming for buildings in high-density urban cities. In: The 2011 Hainan China World Green Roof Conference. 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The multifunctional use of urban greenspace. International Journal of Agricultural Sustainability. 2010;8(1-2):20-25\n'},{id:"B18",body:'Ganguly S et al. Lively’Hood Farm Financial Analysis a Feasibility Study of Commercial Urban Agriculture in the City of San Francisco. Created by: Team Lively’Hood. San Francisco: SF Environment; 2011\n'},{id:"B19",body:'Dika SL, Singh K. Applications of social capital in educational literature: A critical synthesis. Review of Educational Research. 2002;72(1):31-60\n'},{id:"B20",body:'Forrest R, Kearns A. Social cohesion, social capital and the neighbourhood. Urban Studies. 2001;38(12):2125-2143\n'},{id:"B21",body:'Dubos R. Social Capital: Theory and Research. New York: Routledge; 2017\n'},{id:"B22",body:'Doherty K. Urban Agriculture and Ecosystem Services: A Typology and Toolkit for Planners. Amherst: University of Massachusetts Amherst; 2015\n'},{id:"B23",body:'Krishna A, Uphoff NT. Mapping and Measuring Social Capital: A Conceptual and Empirical Study of Collective Action for Conserving and Developing Watersheds in Rajasthan. India: World Bank, Social Development Family, Environmentally and Socially Sustainable Development Network; 1999\n'},{id:"B24",body:'Fan Y-w. Cost-benefit analysis of green roof application in telecommunication building in Hong Kong. [HKU theses Online (HKUTO)]; 2016\n'},{id:"B25",body:'Chui L. Skyrise greenery development in the Hong Kong context. [HKU theses Online (HKUTO)]; 2015\n'},{id:"B26",body:'Luo Y, Li M-H. A study of landscape performance: Do social, economic and environmental benefits always complement each other? Landscape Architecture Frontiers. 2014;2(1):42-57\n'},{id:"B27",body:'Rogler K. Data Farming: Demonstrating the Benefits of Urban Agriculture. 2013 [cited 2018]; Available from: http://thisbigcity.net/data-farming-demonstrating-the-benefits-of-urban-agriculture/\n\n'},{id:"B28",body:'Rahman SRA et al. Perception of green roof as a tool for urban regeneration in a commercial environment: The secret garden, Malaysia. Procedia-Social and Behavioral Sciences. 2015;170:128-136\n'},{id:"B29",body:'Tian Y, Jim C. Development potential of sky gardens in the compact city of Hong Kong. Urban Forestry & Urban Greening. 2012;11(3):223-233\n'},{id:"B30",body:'Pryor M. The Edible Roof: A Guide to Productive Rooftop Gardening. Hong Kong: MCCM Creations; 2016\n'},{id:"B31",body:'Borzaga C, Defourny J. The Emergence of Social Enterprise. Vol. 4. London: Psychology Press; 2004\n'},{id:"B32",body:'Hui M. In Organic-Hungry Hong Kong, Corn as High as an Elevator’s Climb. The New York Times: New york; 2012\n'},{id:"B33",body:'Kahneman D, Knetsch JL. Valuing public goods: The purchase of moral satisfaction. Journal of Environmental Economics and Management. 1992;22(1):57-70\n'},{id:"B34",body:'Allen IE, Seaman CA. Likert scales and data analyses. Quality Progress. 2007;40(7):64\n'},{id:"B35",body:'Government HK. Kwun Tong District Profiles. 2017 [cited 2018 03/04]; Available from: https://www.bycensus2016.gov.hk/en/bc-dp.html\n\n'},{id:"B36",body:'Ahmed US, Gotoh K. Cost-Benefit Analysis of Environmental Goods by Applying Contingent Valuation Method. Tokyo: Springer; 2006\n'},{id:"B37",body:'Fagerholm N, Käyhkö N. Participatory mapping and geographical patterns of the social landscape values of rural communities in Zanzibar, Tanzania. Fennia-International Journal of Geography. 2009;187(1):43-60\n'},{id:"B38",body:'Kim JS et al. Food and the City: A Smarter and Greener Approach towards Urban Regeneration - A Case of Suzhou Industrial Park, China. Shanghai: Xuelin Publishing House; 2018\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Ting Wang",address:"sarahwin@connect.hku.hk",affiliation:'
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\n
1. Introduction
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Chronic Obstructive Pulmonary Disease (COPD) is a common condition, usually affecting people of >40 years of age significantly exposed to noxious particles or gases [1]. Although considered both preventable and treatable [1], COPD remains a leading cause of morbidity and mortality [2, 3], affecting an estimated 384 million people worldwide [4]. The COPD prevalence is projected to increase in the coming decades [5], as well as its position among the leading causes of mortality [4].
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Active or passive cigarette smoking is the most commonly encountered risk factor for COPD across the world [1]; however other factors may play a role in the disease pathogenesis, such as genetic factors [6, 7], exposure to indoor and outdoor air pollutants [8, 9, 10, 11], exposure to occupational dusts, chemical agents or fumes [12], infections (HIV, tuberculosis) [13, 14], and socioeconomic status [15].
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The normal lung response to the inhalation of noxious factors is an inflammatory reaction of the airways. In patients who develop COPD, the excessive inflammatory response is further enhanced by the oxidative stress and an imbalance of the protease-antiprotease system, leading to the destruction of the lung parenchyma and disruption of normal repair and defense mechanisms. Emphysema and small airway fibrosis are the consequences of these processes, which translate into gas trapping and chronic airflow limitation [1].
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By definition, COPD is a chronic condition, and the major symptoms exhibited by the patients suffering from this disease, dyspnea, cough, and sputum production, are usually persistent and/or progressive and have a considerable negative effect on the patient’s quality of life. The Global Burden of Disease Study highlighted that COPD is a major contributor to disability and mortality around the world, by ranking COPD as the fifth leading cause of disability-adjusted life years (DALYs) lost in 2013 [16].
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The natural course of the disease is grafted by acute episodes of worsening of symptoms triggered by infectious agents, air pollution, and other factors. These events are referred to as “exacerbations” and usually require a change in medication and/or hospitalization. Exacerbations are associated with accelerated lung function decline, reduced quality of life, and increased mortality [17] and, not surprisingly, have been surnamed as “chest attacks” or “strokes of the lung” [18, 19].
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2. Pharmacological treatment in stable COPD
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The main goals for the management of stable COPD are improvement in quality of life by relieving symptoms and increasing exercise tolerance and reduction of mortality risk by preventing exacerbations and disease progression [1].
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Several inhaled, oral, and systemically administered drugs improve lung function, decrease the frequency and severity of COPD exacerbations, and improve patients’ quality of life [20].
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Non-pharmacological therapies in COPD, including smoking cessation strategies, pulmonary rehabilitation, vaccinations, surgical or bronchoscopic interventions, and noninvasive ventilation have their established role in the management of the disease; however they are not discussed here, as the focus of this chapter is on the pharmacological treatment.
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Back in 2001 when the first edition of the GOLD document was released [21], the pharmacological arsenal for the treatment of COPD was rather limited, comprising of short-acting beta2-agonists and anticholinergics, long-acting beta2-agonists, theophyllines, and mucoactive agents. Inhaled corticosteroids, although available as single medication, were never widely recommended for the treatment of COPD in monotherapy and have no current authorization for use outside fixed-dose combinations.
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Nowadays, there is a broader range of molecules recommended for the treatment of stable COPD that can be classified in the following classes of pharmacological agents:
Beta2-agonists: short-acting (SABA) and long-acting (LABA)
Anticholinergics: short-acting (SAMA) and long-acting (LAMA)
Additionally, a new acquisition in the bronchodilator portfolio could be the potential use of dual agents or bifunctional muscarinic antagonists and beta2-agonists (MABAs), which combine both antimuscarinic and adrenergic properties in a single molecule [22]. Some of these molecules are already in clinical trials, but a major caveat is the difficulty to balance the antimuscarinic and adrenergic activities, without expressing a tendency toward one of them [23].
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Efforts have been made for the discovery of new pharmacological agents, either belonging to the mentioned classes or addressing new therapeutic targets: new corticosteroids, novel classes of bronchodilators, kinase inhibitors, mediator antagonists (including biological therapies, such as cytokine inhibitors), antioxidants, etc. Unfortunately, many of these molecules never made it to the market or were not granted approval for COPD due to safety, efficacy, or delivery issues; several others are still in the development process [23].
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Currently available pharmacological agents and other therapies are mainly used as pathogenic or symptomatic treatment.
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2.1 Improvement of lung function and symptoms
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Chronic airflow limitation is a central characteristic of COPD and is the result of the combination in varying degrees of several pathological processes such as narrowing of the airways, mucus hypersecretion, and loss of small conducting airways [24]. The consequences of these anatomic changes are expiratory airflow limitation, air trapping, and ventilation-perfusion mismatch [22, 25]. Additionally, the loss of elastic recoil and hyperinflation adversely affect thoracic and diaphragmatic mechanics, increasing the work of breathing and ultimately leading to dynamic hyperinflation [26]. Hyperinflation is an independent predictor of mortality in COPD [27].
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The clinical expression of airflow limitation is chronic, progressive dyspnea, which typically worsens with physical exercise. Chronic cough with or without sputum production is usually a reflection of the ongoing inflammatory process in the airways of COPD patients. However, there is no linear correlation between the severity of the airflow limitation and the level of symptoms. Some patients may have little subjective complaints, although the lung function testing reveals various degrees of airflow limitation, while other patients may have significant complaints, with little or no evidence of airflow obstruction [28]. In some cases, the symptoms may precede the development of airflow limitation by many years [1].
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Treatment with inhaled bronchodilators can reduce hyperinflation, improve dyspnea, and increase exercise tolerance [29], and therefore, bronchodilators are considered as a cornerstone in the management of stable COPD [30].
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While short-acting bronchodilators are an option for patients with occasional dyspnea at low risk of exacerbations, the majority of patients have breathlessness leading to exercise limitation at the time of diagnosis and may require more intensive treatment than short-acting bronchodilators alone [30]. For these patients, whether or not they are also at higher risk of exacerbations, long-acting bronchodilators (as monotherapy or in combination) are recommended as a preferred treatment choice in the GOLD strategy report [1].
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Airway tone is controlled by both the sympathetic and parasympathetic nervous systems. These mechanisms interact and may potentiate each other and are employed alone or in combination therapeutically. Relaxation of airway smooth muscle is caused by blockade of acetylcholine activity at the receptor (muscarinic antagonist) or stimulation of the G protein-coupled receptor (beta-agonist) [31].
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Anticholinergic drugs in the form of smoked alkaloids were among the first effective treatments for asthma [32]. In the mid-twentieth century, parenteral muscarinic antagonists and beta-agonists were used for acute attacks of asthma [33]. The major disadvantages of the systemic delivery were the side effects and a short duration of benefit. As such, subsequent work has both optimized the receptor specificity and the duration of action [22].
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Beta-agonists were in use in Chinese medicine for millennia in the form of ephedra. Developments in the mid-twentieth century yielded compounds that specifically target the beta2-adrenergic receptor, reducing the side effects from beta1-agonists [31].
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Since the approval by the US Food and Drug Administration (FDA) in 2004 of the first LAMA, tiotropium, long-acting bronchodilators have begun to play a central role in the management of stable COPD. Currently available molecules for inhalation delivery are summarized in Table 1.
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Delivery type
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Duration of action (h)
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Long-acting beta2-agonists (LABA)
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Arformoterol
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Nebulized
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12
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Formoterol
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DPI
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12
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Indacaterol
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DPI
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24
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Olodaterol
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SMI
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24
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Salmeterol
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MDI, DPI
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12
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Long-acting anticholinergics (LAMA)
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Aclidinium bromide
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DPI, MDI
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12
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Glycopyrronium bromide
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DPI
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12–24
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\n
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Tiotropium
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DPI, SMI
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24
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Umeclidinium
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DPI
\n
24
\n
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Table 1.
Currently available LABAs and LAMAs as monotherapy.
The benefits of long-acting bronchodilator monotherapy have been well proven across a range of clinical studies [30] and include improvement of the airflow limitation [34, 35, 36, 37, 38, 39], dyspnea [34, 35, 39], physical activity/exercise capacity [29, 40, 41, 42], health status [34, 35, 37, 38, 39], and prevention of exacerbations [35, 39, 43, 44]; however, many patients remain symptomatic despite treatment [45].
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Dual bronchodilation improves lung function compared with a single bronchodilator [30]. Long-acting beta2-agonists and long-acting muscarinic antagonists act via different mechanisms; when used together in patients with COPD, they exert additional bronchodilating effects [46]. Multiple studies have assessed [30] and demonstrated that the use of LABA/LAMA dual bronchodilation results in additional improvements in lung function, exacerbation rates, health status, and other outcome measures when compared with monobronchodilation, while the safety profile of the dual bronchodilators was similar to that observed with placebo and individual monocomponents. Currently available LABA/LAMA combinations are listed in Table 2.
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Delivery type
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Duration of action (h)
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Fixed-dose combinations of LABA and LAMA (LABA/LAMA)
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Formoterol/Aclidinium
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DPI
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12
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Formoterol/Glycopyrronium
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MDI
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12
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Indacaterol/Glycopyrronium
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DPI
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12–24
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Olodaterol/Tiotropium
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SMI
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24
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Vilanterol/Umeclidinium
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DPI
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24
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Table 2.
Currently available fixed-dose combinations of LABA/LAMA.
According to current guidelines and strategy reports, long-acting bronchodilators in monotherapy are adequate options for the majority of COPD patients, regardless of the disease severity. However, in the GOLD report 2019 [1], the authors provide a clarification of the concept of “escalation” and “de-escalation” of the COPD therapy, which was introduced in a previous version. While “de-escalation” is mainly employed for the withdrawal of ICS due to lack of response or side effects, such as pneumonia, the “escalation” of treatment should be prompted by either inappropriate symptomatic response to the initial therapy or by the presence of exacerbations despite regular treatment and consists of adding a second class of bronchodilator and/or an ICS and/or other pharmacological agents (azithromycin, roflumilast) in order to ensure maximal symptom relief and to curb the risk of exacerbations.
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The choice of the bronchodilator treatment should take into account several factors, such as physiological impairment, symptom burden, and exacerbation risk, and should be individualized according to the drug safety profile, cost, and patients’ preference for device and medication [1, 20].
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One of the current controversies in COPD [20] is the following: what is best, a progressive escalation of bronchodilator therapy or “maximizing” bronchodilator therapy with dual bronchodilator therapy ab initio? The members of the GOLD Scientific Committee suggest that ensuring a maximal bronchodilation from the beginning could be a reasonable approach for both patients with high symptom burden and patients less severely affected. The latter may underreport their symptoms, masking an underlying resting and exercise lung hyperinflation, which is further linked to increased mortality and risk of severe exacerbations [20]. However, if a single agent is preferred, currently available evidence supports the use of a LAMA (tiotropium) since it improves lung function and health status even in patients with milder disease [47].
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2.2 Prevention of exacerbations
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COPD exacerbations represent acute worsening of symptoms requiring changes in medication and/or hospitalization [1]. Anthonisen and colleagues’ criteria [48] have been used for decades now in an attempt to standardize the evaluation of these events; however COPD exacerbations still have no universally established definition [49] and are subject to diagnostic uncertainty [50].
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Historically, the level of healthcare resource use (HCRU) required for the management of COPD exacerbations was used both to define and quantify the severity of the exacerbations, with moderate exacerbations requiring administration of oral steroids and/or antibiotics and severe exacerbations requiring hospitalization [49, 51, 52, 53]. However, healthcare use in COPD varies widely depending on access, leading to disparities across different healthcare systems [54]. Furthermore, in order to be treated, an acute event should be reported to healthcare professionals; hence unreported events may not be captured by HCRU definitions. In some reports, such events comprise up to two-thirds of exacerbations and can impair health-related quality of life [55, 56] and increase the risk of hospitalization [57].
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Another approach to define exacerbations is based on the systematic and standardized assessment of daily symptoms recorded using specific questionnaires (diaries) administered to the patients on paper or electronically. These questionnaires were developed with the ability to detect worsening of symptoms beyond a pre-specified threshold, based on patients’ reporting of their daily symptoms [58, 59]. Advantages of a standardized, validated assessment of COPD symptoms in exacerbation studies include uniform metrics, reduced recall bias, and the ability to fully characterize exacerbations of COPD, including the estimated 50–70% of events that are unreported [55, 56, 59]. Although attractive, this kind of approach is more difficult to implement outside the clinical trial setting, and the concordance with the HCRU-defined events is modest [54, 60].
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COPD exacerbations have a marked negative effect on both the patient and underlying disease processes [61] and can result in hospitalization and readmission, an increased risk of death [62], and a significant reduction in health status [55]. Exacerbations are also associated with long-term decline in lung function and a high socioeconomic cost [63, 64]. A history of frequent exacerbations is a good predictor for future exacerbation risk and defines the “frequent exacerbator” phenotype [65]. Thus, optimizing the prevention and management of COPD exacerbations are important clinical issues [61].
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The GOLD strategy report stratifies COPD patients based on the severity of their airflow limitation, symptom burden, and the risk of exacerbations; however the recommendations for the pharmacological treatment rely exclusively on the level of symptoms and exacerbation risk [1].
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While the initial assessment of exacerbation risk may be biased by the patients’ ability to recall historical episodes of symptom worsening prior to being diagnosed with COPD, the reassessment of risk after initial pharmacological treatment should be able to identify patients requiring an escalation of treatment for a better prevention of future exacerbation episodes.
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The preferred treatment options for patients at high risk of exacerbation are a LAMA in monotherapy, a LABA/LAMA, or a LABA/ICS combination [1].
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There is evidence that both LABAs and LAMAs significantly improve the exacerbation rate versus placebo [66, 67, 68]; however, clinical trials have shown a greater effect on exacerbation rates for LAMA treatment (tiotropium) versus LABA treatment [69, 70].
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There is a strong evidence that treatment with fixed-dose combinations of LABA/LAMA improves lung function, symptoms, and health-related quality of life compared to placebo or its individual bronchodilator components [71, 72, 73]. The superiority of dual bronchodilation in the prevention of exacerbations compared to monocomponents was demonstrated for a LABA/LAMA combination [74], while another large study found that combining a LABA with a LAMA did not reduce exacerbation rate as much as expected compared to LAMA alone [75].
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Similarly, an ICS combined with a LABA is more effective than the individual components in improving lung function and health status and reducing exacerbations in patients with a history of exacerbations and moderate to very severe COPD [76, 77]. Currently available ICS/LABA combinations are listed in Table 3.
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Delivery type
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Duration of action (h)
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Fixed-dose combinations of LABA and ICS (LABA/ICS)
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Formoterol/Beclometasone
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MDI
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12
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Formoterol/Budesonide
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MDI, DPI
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12
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Formoterol/Mometasone
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MDI
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12
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Salmeterol/Fluticasone
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MDI, DPI
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12
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Vilanterol/Fluticasone furoate
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DPI
\n
24
\n
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Table 3.
Currently available fixed-dose combinations of LABA/ICS.
Furthermore, another study demonstrated the superiority of a LABA/LAMA combination versus an ICS/LABA combination in the prevention of exacerbations in patients with moderate to very severe COPD and a history of exacerbations, regardless of baseline blood eosinophils [78].
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In a recently published review, a group of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single long-acting bronchodilators or LABA/inhaled corticosteroids in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impaired mucociliary clearance, and symptom severity [79].
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Although triple therapy in separate inhalers is already in use for COPD patients for a couple of years now, fixed triple therapy combining an ICS, a LABA, and a LAMA in a single inhaler recently emerged on the market. Currently, there are only two products approved by the European Medicines Agency (EMA) for use in COPD, and a third one was recently approved in Japan (see Table 4) [80].
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Delivery type
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Duration of action (h)
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Fixed-dose combinations of LABA, LAMA and ICS (LABA/LAMA/ICS)
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Formoterol/Glycopyrronium/Beclometasone
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MDI
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12
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Vilanterol/Umeclidinium/Fluticasone furoate
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DPI
\n
24
\n
\n
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Formoterol/Glycopyrronium/Budesonide
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MDI
\n
12
\n
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Table 4.
Currently available fixed-dose combinations of LABA/LAMA/ICS.
Several recent studies have demonstrated that single-inhaler triple therapy is more effective in reducing the exacerbation than LAMA alone, a LABA/ICS, or a LABA/LAMA combination [81, 82, 83, 84].
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The GOLD algorithm for the escalation of treatment in patients with persistent risk of exacerbations despite regular treatment provides that patients taking a single bronchodilator should be switched to dual bronchodilation and then to triple therapy and/or additional therapies. Alternatively, some patients with high blood eosinophils may benefit from a LABA/ICS combination prior to receiving triple therapy [1].
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The use of ICS in COPD has become very controversial in the last years, owing on the one hand to the limited effect on lung function and on the other hand to potential side effects associated with long-term use at the higher doses recommended for the treatment of COPD. These include:
Risk of infections such as pneumonia [85], tuberculosis and non-tuberculous mycobacterial disease [86], and oropharyngeal candidiasis [87]
The use of ICS alone is discouraged in COPD [20]; however several studies have demonstrated a consistent effect on exacerbation reduction of LABA/ICS fixed-dose combinations versus individual monocomponents [76, 77, 87, 92, 93].
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The need for biomarkers accurately assessing disease activity and response to therapy in order to develop better COPD treatment is well acknowledged [94]. Peripheral blood eosinophil level has emerged in the recent years as a promising biomarker, showing capabilities to predict both the risk of exacerbation and the magnitude of response to ICS therapy [95, 96, 97]. Thus, several post hoc or pre-specified analyses of clinical trials have shown that blood eosinophil levels may indicate which patients can benefit from a reduction of exacerbations by the treatment with ICS-containing regimens [84, 96, 98]. Various cutoff points were proposed for the level of blood eosinophils in order to identify the patients who would benefit most from the ICS therapy. A recent pooled analysis (n = 4528) evidenced that a level of blood eosinophils >300/mmc3 suggests a beneficial role of ICS, while a low level of blood eosinophils (<100/mmc3) may be a negative predictor of the ICS effects. This was previously observed in other two post hoc analyses [99, 100] and was confirmed in a pre-specified analysis of another randomized clinical trial [101].
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Other classes of pharmacological agents, such as PDE4-inhibitors (roflumilast) or antibiotics (azithromycin) administered orally on top of inhaled therapy, may bring an additional benefit in reducing exacerbations [102, 103]. The side effects, however, limit their use to selected patients only.
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2.3 Mortality risk
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Two large clinical trials have failed to demonstrate a positive effect of the active treatments (LABA/ICS, ICS alone, and LABA alone) versus placebo on the mortality risk [36, 104].
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Smoking cessation, vaccinations, supplemental oxygen for hypoxemic patients, and lung volume reduction surgery in selected patients are the only therapies that have been proven to improve survival; smoking cessation also attenuates disease progression [20].
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3. Conclusions
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Inhaled long-acting bronchodilator treatment plays a central role in the management of stable COPD. Anti-inflammatory treatment with inhaled corticosteroids in combination with a long-acting beta2 agonist or with dual bronchodilation (LABA and LAMA) as part of the triple therapy improves outcomes especially in patients with high blood eosinophil level.
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Despite all the progress made in the recent years in the field of COPD, we are still lacking drugs that can effectively modify the course of the disease [23].
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The unmet needs in COPD warrant further research for the discovery of new biomarkers and effective therapeutic agents able to radically improve short-term and long-term outcomes in patients suffering of this disease.
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\n\n',keywords:"COPD, lung function, exacerbation, bronchodilators, corticosteroids, biomarkers, eosinophils",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/70075.pdf",chapterXML:"https://mts.intechopen.com/source/xml/70075.xml",downloadPdfUrl:"/chapter/pdf-download/70075",previewPdfUrl:"/chapter/pdf-preview/70075",totalDownloads:201,totalViews:0,totalCrossrefCites:0,dateSubmitted:"June 11th 2019",dateReviewed:"October 22nd 2019",datePrePublished:"February 5th 2020",datePublished:null,dateFinished:null,readingETA:"0",abstract:"Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and mortality worldwide. Although it is considered both preventable and treatable, COPD still represents an important public health challenge. The classes of pharmacological agents widely used for the maintenance treatment are bronchodilators (SABA, SAMA, LABA, LAMA) and inhaled corticosteroids (ICS). While it is largely accepted that inhaled bronchodilators, which are effective and well tolerated in patients with stable disease, are the cornerstone of the pharmacological management of COPD, there is an ongoing debate regarding the role of inhaled corticosteroids. This is also reflected in the last versions of the GOLD recommendations, which suffered dramatic changes in the recent years. The trend for personalized medicine led to the search for biomarkers which could guide the therapeutic decisions. Recent studies demonstrated that blood eosinophils can reasonably predict the ICS relative efficacy in preventing COPD exacerbations and thus could inform the disease management.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/70075",risUrl:"/chapter/ris/70075",signatures:"Stefan-Marian Frent",book:{id:"7990",title:"Update in Respiratory Diseases",subtitle:null,fullTitle:"Update in Respiratory Diseases",slug:"update-in-respiratory-diseases",publishedDate:"December 2nd 2020",bookSignature:"Jose Carlos Herrera Garcia",coverURL:"https://cdn.intechopen.com/books/images_new/7990.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"224037",title:"Dr.",name:"Jose Carlos",middleName:null,surname:"Herrera Garcia",slug:"jose-carlos-herrera-garcia",fullName:"Jose Carlos Herrera Garcia"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Pharmacological treatment in stable COPD",level:"1"},{id:"sec_2_2",title:"2.1 Improvement of lung function and symptoms",level:"2"},{id:"sec_3_2",title:"2.2 Prevention of exacerbations",level:"2"},{id:"sec_4_2",title:"2.3 Mortality risk",level:"2"},{id:"sec_6",title:"3. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'\nSingh D, Agusti A, Anzueto A, Barnes PJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease: The GOLD science committee report 2019. The European Respiratory Journal. 2019;53(5):pii: 1900164. DOI: 10.1183/13993003.00164-2019\n'},{id:"B2",body:'\nLozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the global burden of disease study 2010. Lancet. 2012;380(9859):2095-2128\n'},{id:"B3",body:'\nVos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2163-2196\n'},{id:"B4",body:'\nAdeloye D, Chua S, Lee C, et al. Global and regional estimates of COPD prevalence: Systematic review and meta-analysis. Journal of Global Health. 2015;5:020415\n'},{id:"B5",body:'\nMathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Medicine. 2006;3(11):e442\n'},{id:"B6",body:'\nStoller JK, Aboussouan LS. Alpha1-antitrypsin deficiency. Lancet. 2005;365(9478):2225-2236\n'},{id:"B7",body:'\nMcCloskey SC, Patel BD, Hinchliffe SJ, Reid ED, Wareham NJ, Lomas DA. Siblings of patients with severe chronic obstructive pulmonary disease have a significant risk of airflow obstruction. American Journal of Respiratory and Critical Care Medicine. 2001;164(8 Pt 1):1419-1424\n'},{id:"B8",body:'\nEisner MD, Anthonisen M, Coultas D, et al. An official American Thoracic Society public policy statement: Novel risk factors and the global burden of chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine. 2010;182(5):693-718\n'},{id:"B9",body:'\nEzzati M. Indoor air pollution and health in developing countries. Lancet. 2005;366(9480):104-106\n'},{id:"B10",body:'\nAssad NA, Balmes J, Mehta S, Cheema U, Sood A. Chronic obstructive pulmonary disease secondary to household air pollution. Seminars in Respiratory and Critical Care Medicine. 2015;36(3):408-421\n'},{id:"B11",body:'\nLiu S, Zhou Y, Liu S, et al. Association between exposure to ambient particulate matter and chronic obstructive pulmonary disease: Results from a cross-sectional study in China. Thorax. 2017;72(9):788-795\n'},{id:"B12",body:'\nBalmes J, Becklake M, Blanc P, et al. American Thoracic Society statement: Occupational contribution to the burden of airway disease. American Journal of Respiratory and Critical Care Medicine. 2003;167(5):787-797\n'},{id:"B13",body:'\nBigna JJ, Kenne AM, Asangbeh SL, Sibetcheu AT. Prevalence of chronic obstructive pulmonary disease in the global population with HIV: A systematic review and meta-analysis. The Lancet Global Health. 2018;6(2):e193-e202\n'},{id:"B14",body:'\nByrne AL, Marais BJ, Mitnick CD, Lecca L, Marks GB. Tuberculosis and chronic respiratory disease: A systematic review. International Journal of Infectious Diseases. 2015;32:138-146\n'},{id:"B15",body:'\nTownend J, Minelli C, Mortimer K, et al. The association between chronic airflow obstruction and poverty in 12 sites of the multinational BOLD study. The European Respiratory Journal. 2017;49(6):pii: 1601880\n'},{id:"B16",body:'\nGBD 2013 DALYs and HALE Collaborators, Murray CJ, Barber RM, et al. Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition. Lancet. 2015;386(10009):2145-2191\n'},{id:"B17",body:'\nHalpin DM, Decramer M, Celli B, Kesten S, Liu D, Tashkin DP. Exacerbation frequency and course of COPD. International Journal of Chronic Obstructive Pulmonary Disease. 2012;7:653-661\n'},{id:"B18",body:'\nCelli BR. Dissecting COPD exacerbations: Time to rethink our definition. The European Respiratory Journal. 2017;50:1701432\n'},{id:"B19",body:'\nHillas G, Perlikos F, Tzanakis N. Acute exacerbation of COPD: Is it the “stroke of the lungs”? International Journal of Chronic Obstructive Pulmonary Disease. 2016;11:1579-1586\n'},{id:"B20",body:'\nCriner GJ, Martinez FJ, et al. Current controversies in chronic obstructive pulmonary disease. A report from the Global Initiative for Chronic Obstructive Lung Disease Scientific Committee. Annals of the American Thoracic Society. 2019;16(1):29-39\n'},{id:"B21",body:'\nPauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS, GOLD Scientific Committee. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative For Chronic Obstructive Lung Disease (GOLD) Workshop summary. American Journal of Respiratory and Critical Care Medicine. 2001;163(5):1256-1276\n'},{id:"B22",body:'\nCohen JS, Miles MC, Donohue JF, Ohar JA. Dual therapy strategies for COPD: The scientific rationale for LAMA + LABA. International Journal of Chronic Obstructive Pulmonary Disease. 2016;11:785-797\n'},{id:"B23",body:'\nGross NJ, Barnes PJ. New therapies for asthma and chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine. 2017;195(2):159-166\n'},{id:"B24",body:'\nMcDonough JE, Yuan R, Suzuki M, et al. Small-airway obstruction and emphysema in chronic obstructive pulmonary disease. The New England Journal of Medicine. 2011;365(17):1567-1575\n'},{id:"B25",body:'\nSenior R, Atkinson J. Chronic obstructive pulmonary disease: Epidemiology, pathophysiology, and pathogenesis. In: Alfred Fishman M, editor. Fishman’s Pulmonary Diseases and Disorders. 4th ed. Vol. 1. New York, NY: McGraw Hill Medical; 2008. pp. 707-728\n'},{id:"B26",body:'\nO’Donnell DE, Laveneziana P. Physiology and consequences of lung hyperinflation in COPD. European Respiratory Review. 2006;15(100):61-67\n'},{id:"B27",body:'\nCasanova C, Cote C, de Torres JP, et al. Inspiratory-to-total lung capacity ratio predicts mortality in patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine. 2005;171(6):591-597\n'},{id:"B28",body:'\nMontes de Oca M, Perez-Padilla R, Talamo C, et al. Acute bronchodilator responsiveness in subjects with and without airflow obstruction in five Latin American cities: The PLATINO study. Pulmonary Pharmacology & Therapeutics. 2010;23(1):29-35\n'},{id:"B29",body:'\nO’Donnell DE, Fluge T, Gerken F, et al. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. The European Respiratory Journal. 2004;23(6):832-840\n'},{id:"B30",body:'\nThomas M, Halpin D, Miravitlles M. When is dual bronchodilation indicated in COPD? International Journal of Chronic Obstructive Pulmonary Disease. 2017;12:2291-2305\n'},{id:"B31",body:'\nCazzola M, Page CP, Calzetta L, Matera MG. Pharmacology and therapeutics of bronchodilators. Pharmacological Reviews. 2012;64(3):450-504\n'},{id:"B32",body:'\nJackson M. “Divine stramonium”: The rise and fall of smoking for asthma. Medical History. 2010;54(2):171-194\n'},{id:"B33",body:'\nBray GW. The treatment of asthma. British Medical Journal. 1935;1(3863):119-121\n'},{id:"B34",body:'\nDonohue JF, van Noord JA, Bateman ED, et al. A 6-month, placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol. Chest. 2002;122(1):47-55\n'},{id:"B35",body:'\nD’Urzo A, Ferguson GT, van Noord JA, et al. Efficacy and safety of once-daily NVA237 in patients with moderate-to-severe COPD: The GLOW1 trial. Respiratory Research. 2011;12:156\n'},{id:"B36",body:'\nCalverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. The New England Journal of Medicine. 2007;356(8):775-789\n'},{id:"B37",body:'\nRossi A, Kristufek P, Levine BE, et al. Comparison of the efficacy, tolerability, and safety of formoterol dry powder and oral, slow-release theophylline in the treatment of COPD. Chest. 2002;121(4):1058-1069\n'},{id:"B38",body:'\nChapman KR, Rennard SI, Dogra A, et al. Long-term safety and efficacy of indacaterol, a long-acting β2-agonist, in subjects with COPD: A randomized, placebo-controlled study. Chest. 2011;140(1):68-75\n'},{id:"B39",body:'\nKerwin EM, D’Urzo AD, Gelb AF, Lakkis H, Garcia GE, Caracta CF. Efficacy and safety of a 12-week treatment with twice-daily aclidinium bromide in COPD patients (ACCORD COPD I). COPD. 2012;9(2):90-101\n'},{id:"B40",body:'\nBeeh KM, Singh D, Di Scala L, Drollmann A. Once-daily NVA237 improves exercise tolerance from the first dose in patients with COPD: The GLOW3 trial. International Journal of Chronic Obstructive Pulmonary Disease. 2012;7:503-513\n'},{id:"B41",body:'\nMaltais F, Celli B, Casaburi R, et al. Aclidinium bromide improves exercise endurance and lung hyperinflation in patients with moderate to severe COPD. Respiratory Medicine. 2011;105(4):580-587\n'},{id:"B42",body:'\nO’Donnell DE, Casaburi R, Vincken W, et al. Effect of indacaterol on exercise endurance and lung hyperinflation in COPD. Respiratory Medicine. 2011;105(7):1030-1036\n'},{id:"B43",body:'\nHalpin DM, Vogelmeier C, Pieper MP, Metzdorf N, Richard F, Anzueto A. Effect of tiotropium on COPD exacerbations: A systematic review. Respiratory Medicine. 2016;114:1-8\n'},{id:"B44",body:'\nJones PW, Singh D, Bateman ED, et al. Efficacy and safety of twice-daily aclidinium bromide in COPD patients: The ATTAIN study. The European Respiratory Journal. 2012;40(4):830-836\n'},{id:"B45",body:'\nPrice D, West D, Brusselle G, et al. Management of COPD in the UK primary-care setting: An analysis of real-life prescribing patterns. International Journal of Chronic Obstructive Pulmonary Disease. 2014;9:889-905\n'},{id:"B46",body:'\nTashkin DP, Ferguson GT. Combination bronchodilator therapy in the management of chronic obstructive pulmonary disease. Respiratory Research. 2013;14:49\n'},{id:"B47",body:'\nZhou Y, Zhong NS, Li X, et al. Tiotropium in early-stage chronic obstructive pulmonary disease. The New England Journal of Medicine. 2017;377:923-935\n'},{id:"B48",body:'\nAnthonisen NR, Manfreda J, Warren CP, Hershfield ES, Harding GK, Nelson NA. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Annals of Internal Medicine. 1987;106:196-204\n'},{id:"B49",body:'\nRodriguez-Roisin R. Toward a consensus definition for COPD exacerbations. Chest. 2000;117:398s-401s\n'},{id:"B50",body:'\nSapey E, Stockley RA. COPD exacerbations. 2: Aetiology. Thorax. 2006;61:250-258\n'},{id:"B51",body:'\nBurge S, Wedzicha JA. COPD exacerbations: Definitions and classifications. The European Respiratory Journal. Supplement. 2003;41:46s-53s\n'},{id:"B52",body:'\nCalverley P, Pauwels Dagger R, Lofdahl CG, Svensson K, Higenbottam T, Carlsson LG, et al. Relationship between respiratory symptoms and medical treatment in exacerbations of COPD. The European Respiratory Journal. 2005;26:406-413\n'},{id:"B53",body:'\nWedzicha JA, Seemungal TA. COPD exacerbations: Defining their cause and prevention. Lancet. 2007;370(9589):786-796\n'},{id:"B54",body:'\nFrent SM, Chapman KR, et al. Capturing exacerbations of chronic obstructive pulmonary disease with EXACT. A subanalysis of FLAME. American Journal of Respiratory and Critical Care Medicine. 2019;199(1):43-51\n'},{id:"B55",body:'\nSeemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine. 1998;157:1418-1422\n'},{id:"B56",body:'\nLangsetmo L, Platt RW, Ernst P, Bourbeau J. Underreporting exacerbation of chronic obstructive pulmonary disease in a longitudinal cohort. American Journal of Respiratory and Critical Care Medicine. 2008;177:396-401\n'},{id:"B57",body:'\nWilkinson TM, Donaldson GC, Hurst JR, Seemungal TA, Wedzicha JA. Early therapy improves outcomes of exacerbations of chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine. 2004;169:1298-1303\n'},{id:"B58",body:'\nKulich K, Keininger DL, Tiplady B, Banerji D. Symptoms and impact of COPD assessed by an electronic diary in patients with moderate-to-severe COPD: Psychometric results from the SHINE study. International Journal of Chronic Obstructive Pulmonary Disease. 2015;10:79-94\n'},{id:"B59",body:'\nLeidy NK, Wilcox TK, Jones PW, Murray L, Winnette R, Howard K, et al. Development of the EXAcerbations of chronic obstructive pulmonary disease tool (EXACT): A patient-reported outcome (PRO) measure. Value in Health. 2010;13:965-975\n'},{id:"B60",body:'\nJones PW, Lamarca R, Chuecos F, Singh D, Agusti A, Bateman ED, et al. Characterisation and impact of reported and unreported exacerbations: Results from ATTAIN. The European Respiratory Journal. 2014;44:1156-1165\n'},{id:"B61",body:'\nMarc Miravitlles M, Anzueto A, Jardim JR. Optimizing bronchodilation in the prevention of COPD exacerbations. Respiratory Research. 2017;18(1):125\n'},{id:"B62",body:'\nSoler-Cataluña JJ, Martínez-García MA, Román Sánchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005;60:925-931\n'},{id:"B63",body:'\nDonaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA. Relationship between exacerbation frequency and lung function decline in chronicobstructive pulmonary disease. Thorax. 2002;57:847-852\n'},{id:"B64",body:'\nDhamane AD, Moretz C, Zhou Y, Burslem K, Saverno K, Jain G, et al. COPD exacerbation frequency and its association with health care resource utilization and costs. International Journal of Chronic Obstructive Pulmonary Disease. 2015;10:2609-2618\n'},{id:"B65",body:'\nHurst JR, Vestbo J, Anzueto A, Locantore N, Müllerova H, Tal-Singer R, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. The New England Journal of Medicine. 2010;363:1128-1138\n'},{id:"B66",body:'\nKew KM, Mavergames C, Walters JA. Long-acting beta2-agonists for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews. 2013;10:CD010177\n'},{id:"B67",body:'\nGeake JB, Dabscheck EJ, Wood-Baker R, Cates CJ. Indacaterol, a once-daily beta2-agonist, versus twice-daily beta₂-agonists or placebo for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews. 2015;1:CD010139\n'},{id:"B68",body:'\nKarner C, Chong J, Poole P. Tiotropium versus placebo for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews. 2014;7(7):CD009285\n'},{id:"B69",body:'\nVogelmeier C, Hederer B, Glaab T, et al. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. The New England Journal of Medicine. 2011;364(12):1093-1103\n'},{id:"B70",body:'\nDecramer ML, Chapman KR, Dahl R, et al. Once-daily indacaterol versus tiotropium for patients with severe chronic obstructive pulmonary disease (INVIGORATE): A randomised, blinded, parallel-group study. The Lancet Respiratory Medicine. 2013;1(7):524-533\n'},{id:"B71",body:'\nMahler DA, Decramer M, D\'Urzo A, et al. Dual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: The BLAZE study. The European Respiratory Journal. 2014;43(6):1599-1609\n'},{id:"B72",body:'\nSingh D, Ferguson GT, Bolitschek J, et al. Tiotropium + olodaterol shows clinically meaningful improvements in quality of life. Respiratory Medicine. 2015;109(10):1312-1319\n'},{id:"B73",body:'\nBateman ED, Chapman KR, Singh D, et al. Aclidinium bromide and formoterol fumarate as a fixed-dose combination in COPD: Pooled analysis of symptoms and exacerbations from two six-month, multicentre, randomised studies (ACLIFORM and AUGMENT). Respiratory Research. 2015;16:92\n'},{id:"B74",body:'\nWedzicha JA, Decramer M, Ficker JH, et al. Analysis of chronic obstructive pulmonary disease exacerbations with the dual bronchodilator QVA149 compared with glycopyrronium and tiotropium (SPARK): A randomised, double-blind, parallel-group study. The Lancet Respiratory Medicine. 2013;1(3):199-209\n'},{id:"B75",body:'\nCalverley PMA, Anzueto AR, Carter K, et al. Tiotropium and olodaterol in the prevention of chronic obstructive pulmonary disease exacerbations (DYNAGITO): A double-blind, randomised, parallel-group, active-controlled trial. The Lancet Respiratory Medicine. 2018;6(5):337-344\n'},{id:"B76",body:'\nNannini LJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews. 2012;9(9):CD006829\n'},{id:"B77",body:'\nNannini LJ, Poole P, Milan SJ, Kesterton A. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus inhaled corticosteroids alone for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews. 2013;8(8):CD006826\n'},{id:"B78",body:'\nWedzicha JA, Banerji D, Chapman KR, et al. Indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD. The New England Journal of Medicine. 2016;374(23):2222-2234\n'},{id:"B79",body:'\nBeeh KM, Burgel PR, Franssen FME, et al. How do dual long-acting bronchodilators prevent exacerbations of chronic obstructive pulmonary disease? American Journal of Respiratory and Critical Care Medicine. 2017;196(2):139-149\n'},{id:"B80",body:'\nAstraZeneca. Breztri Aerosphere (PT010) Approved in Japan for Patients with Chronic Obstructive Pulmonary Disease [Internet]. 2019. Available from: https://www.astrazeneca.com/media-centre/press-releases/2019/breztri-aerosphere-pt010-approved-in-japan-for-patients-with-chronic-obstructive-pulmonary-disease-19062019.html [Accessed: September 18, 2019]\n'},{id:"B81",body:'\nVestbo J, Papi A, Corradi M, et al. Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): A double-blind, parallel group, randomised controlled trial. Lancet. 2017;389(10082):1919-1929\n'},{id:"B82",body:'\nSingh D, Papi A, Corradi M, et al. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting β2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): A double-blind, parallel group, randomised controlled trial. Lancet. 2016;388:963-973\n'},{id:"B83",body:'\nPapi A, Vestbo J, Fabbri L, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): A double-blind, parallel group, randomised controlled trial. Lancet. 2018;391(10125):1076-1084\n'},{id:"B84",body:'\nLipson DA, Barnhart F, Brealey N, et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. The New England Journal of Medicine. 2018;378(18):1671-1680\n'},{id:"B85",body:'\nKew KM, Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews. 2014;10:CD010115\n'},{id:"B86",body:'\nBrode SK, Campitelli MA, Kwong JC, et al. The risk of mycobacterial infections associated with inhaled corticosteroid use. The European Respiratory Journal. 2017;50:pii: 1700037\n'},{id:"B87",body:'\nDransfield MT, Bourbeau J, Jones PW, et al. Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: Two replicate double-blind, parallel-group, randomised controlled trials. The Lancet Respiratory Medicine. 2013;1:210-223\n'},{id:"B88",body:'\nPrice D, Yawn B, Brusselle G, Rossi A. Risk-to-benefit ratio of inhaled corticosteroids in patients with COPD. Primary Care Respiratory Journal. 2013;22:92-100\n'},{id:"B89",body:'\nSuissa S, Kezouh A, Ernst P. Inhaled corticosteroids and the risks of diabetes onset and progression. The American Journal of Medicine. 2010;123:1001-1006\n'},{id:"B90",body:'\nGonzalez AV, Coulombe J, Ernst P, Suissa S. Long-term use of inhaled corticosteroids in COPD and the risk of fracture. Chest. 2017;153(2):321-328\n'},{id:"B91",body:'\nCumming RG, Mitchell P, Leeder SR. Use of inhaled corticosteroids and the risk of cataracts. The New England Journal of Medicine. 1997;337(1):8-14\n'},{id:"B92",body:'\nCalverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: A randomised controlled trial. Lancet. 2003;361:449-456\n'},{id:"B93",body:'\nSharafkhaneh A, Southard JG, Goldman M, Uryniak T, Martin UJ. Effect of budesonide/formoterol pMDI on COPD exacerbations: A double-blind, randomized study. Respiratory Medicine. 2012;106(2):257-268\n'},{id:"B94",body:'\nMannino DM. Biomarkers in COPD: The search continues! The European Respiratory Journal. 2015;45:872-874\n'},{id:"B95",body:'\nVedel-Krogh S, Nielsen SF, Lange P, Vestbo J, Nordestgaard BG. Blood eosinophils and exacerbations in chronic obstructive pulmonary disease. The Copenhagen general population study. American Journal of Respiratory and Critical Care Medicine. 2016;193:965-974\n'},{id:"B96",body:'\nPascoe S, Locantore N, Dransfield MT, Barnes NC, Pavord ID. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: A secondary analysis of data from two parallel randomised controlled trials. The Lancet Respiratory Medicine. 2015;3(6):435-442\n'},{id:"B97",body:'\nBafadhel M, Peterson S, De Blas MA, et al. Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: A post-hoc analysis of three randomised trials. The Lancet Respiratory Medicine. 2018;6(2):117-126\n'},{id:"B98",body:'\nSiddiqui SH, Guasconi A, Vestbo J, Jones P, Agusti A, Paggiaro P, et al. Blood eosinophils: A biomarker of response to extrafine beclomethasone/formoterol in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine. 2015;192:523-525\n'},{id:"B99",body:'\nWatz H, Tetzlaff K, Wouters EF, et al. Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: A post-hoc analysis of the WISDOM trial. The Lancet Respiratory Medicine. 2016;4:390-398\n'},{id:"B100",body:'\nRoche N, Chapman KR, Vogelmeier CF, et al. Blood eosinophils and response to maintenance chronic obstructive pulmonary disease treatment. Data from the FLAME Trial. American Journal of Respiratory and Critical Care Medicine. 2017;195:1189-1197\n'},{id:"B101",body:'\nChapman KR, Hurst JR, Frent SM, et al. Long-term triple therapy de-escalation to indacaterol/glycopyrronium in patients with chronic obstructive pulmonary disease (SUNSET): A randomized, double-blind, triple-dummy clinical trial. American Journal of Respiratory and Critical Care Medicine. 2018;198(3):329-339\n'},{id:"B102",body:'\nCalverley PM, Rabe KF, Goehring UM, et al. Roflumilast in symptomatic chronic obstructive pulmonary disease: Two randomised clinical trials. Lancet. 2009;374(9691):685-694\n'},{id:"B103",body:'\nUzun S, Djamin RS, Kluytmans JA, et al. Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): A randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine. 2014;2(5):361-368\n'},{id:"B104",body:'\nVestbo J, Anderson JA, Brook RD, et al. Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): A double-blind randomised controlled trial. Lancet. 2016;387(10030):1817-1826\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Stefan-Marian Frent",address:"frentz.stefan@umft.ro",affiliation:'
Department of Pulmonology, University of Medicine and Pharmacy Timisoara, Timisoara, Romania
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\\n\\n
If your manuscript:
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\\n\\t
Exceeds 20 pages (for chapters in Edited Volumes), an additional fee of 40 GBP per page will be required
\\n\\t
If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
\\n
\\n\\n
Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
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Open Access Funding
\\n\\n
To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at oapf@intechopen.com for further details or assistance.
\\n\\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\\n\\n
Added Value of Publishing with IntechOpen
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Choosing to publish with IntechOpen ensures the following benefits:
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\\n\\t
Indexing and listing across major repositories, see details ...
\\n\\t
Long-term archiving
\\n\\t
Visibility on the world's strongest OA platform
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Live Performance Metrics to track readership and the impact of your chapter
\\n\\t
Dissemination and Promotion
\\n
\\n\\n
Benefits of Publishing with IntechOpen
\\n\\n
\\n\\t
Proven world leader in Open Access book publishing with over 10 years experience
\\n\\t
+4,800 OA books published
\\n\\t
Most competitive prices in the market
\\n\\t
Fully compliant with OA funding requirements
\\n\\t
Optimized processes, enabling publication between 8 and 12 months
\\n\\t
Personal support during every step of the publication process
\\n\\t
+146,150 citations in Web of Science databases
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Currently strongest OA platform with over 130 million downloads
As a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 118,000 international scientists and researchers.
\n\n
The Open Access Publishing Fee (OAPF) is payable only after your full chapter, monograph or Compacts monograph is accepted for publication.
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OAPF Publishing Options
\n\n
\n\t
1,400 GBP Chapter - Edited Volume
\n\t
10,000 GBP Monograph - Long Form
\n\t
4,000 GBP Compacts Monograph - Short Form
\n
\n\n
*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
\n\n
Services included are:
\n\n
\n\t
An online manuscript tracking system to facilitate your work
\n\t
Personal contact and support throughout the publishing process from your dedicated Author Service Manager
\n\t
Assurance that your manuscript meets the highest publishing standards
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English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
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XML Typesetting and pagination - web (PDF, HTML) and print files preparation
\n\t
Discoverability - electronic citation and linking via DOI
\n\t
Permanent and unrestricted online access to your work
What isn't covered by the Open Access Publishing Fee?
\n\n
If your manuscript:
\n\n
\n\t
Exceeds 20 pages (for chapters in Edited Volumes), an additional fee of 40 GBP per page will be required
\n\t
If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
\n
\n\n
Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\n\n
Open Access Funding
\n\n
To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at oapf@intechopen.com for further details or assistance.
\n\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\n\n
Added Value of Publishing with IntechOpen
\n\n
Choosing to publish with IntechOpen ensures the following benefits:
\n\n
\n\t
Indexing and listing across major repositories, see details ...
\n\t
Long-term archiving
\n\t
Visibility on the world's strongest OA platform
\n\t
Live Performance Metrics to track readership and the impact of your chapter
\n\t
Dissemination and Promotion
\n
\n\n
Benefits of Publishing with IntechOpen
\n\n
\n\t
Proven world leader in Open Access book publishing with over 10 years experience
\n\t
+4,800 OA books published
\n\t
Most competitive prices in the market
\n\t
Fully compliant with OA funding requirements
\n\t
Optimized processes, enabling publication between 8 and 12 months
\n\t
Personal support during every step of the publication process
\n\t
+146,150 citations in Web of Science databases
\n\t
Currently strongest OA platform with over 130 million downloads
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