Criteria for diagnosing IPF exacerbation as per working group idiopathic pulmonary fibrosis network (IPF net).
\r\n\tFurthermore, during the preparation of high-quality dairy products, several physical, chemical, enzymatic, and microbial transformations take place. We will consciously focus on this interaction of different constituents of milk under different processing conditions for the development of the products.
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The IPF is more common among males and in the elderly age group [1]. Although the exact etiology of AE-IPF is unknown, there are many important risk factors as well as triggers that have been identified. There is associated accelerated decline in lung function which leads to poor prognosis [1]. It is estimated that about 35 to 46% of deaths in IPF are caused by AE-IPF [2]. In hospital mortality is more than 50% and follow up after hospitalization shows a mortality up to 73% at the end of 90 days [2, 3]. Although treatment with high dose Gluco corticoids have been used extensively, there is lack of controlled well designed trials to support its use and in fact survival has been shown to be decreased with steroids and or other immune suppressants [4, 5]. Some newer anti-fibrotic agents like Pirfenidone and Nintedanib may improve survival, the latter may be helpful in preventing AE-IPF [1, 6, 7].
Acute exacerbation of IPF is recognized with the help of a set of criteria laid out by the International IPF Working group network which is as follows [2, 4, 8, 9, 10, 11, 12].
“An acute, clinically significant respiratory deterioration characterized by evidence of new widespread alveolar abnormality”.
The following four diagnostic criteria have to be met as shown in Table 1.
A known or concurrent diagnosis of IPF |
Clinical respiratory deterioration noted “typically” in the preceding 30 days. |
Presence of typical UIP pattern on CT chest including bilateral basilar reticular changes with honeycombing and traction bronchiectasis. Superimposed ground glass attenuation and /or consolidation is necessary in exacerbation. When possible specific UIP pattern may be combined with histopathological information to make a more robust diagnosis. |
Absence of heart failure, Pulmonary embolism, fluid overload or any other differential pathology. |
Note that endotracheal aspirate is not necessary as per new diagnostic criteria. |
The 30-day time limit of clinical deterioration is not strictly enforced. |
Exclude other causes of Interstitial Lung disease such as drug toxicity, connective tissue disease, hypersensitivity pneumonitis, etc. |
Criteria for diagnosing IPF exacerbation as per working group idiopathic pulmonary fibrosis network (IPF net).
The guidelines also provided certain clarifications that help in making a diagnosis [11].
Events that are clinically considered to meet the definition of acute exacerbation of IPF but fail to meet all four diagnostic criteria owing to missing computed tomography data are to be termed “suspected acute exacerbations.” For example, if CT scan shows unilateral ground glass attenuation or data available is incomplete [2].
If the diagnosis of IPF is not previously established, this criterion can be met by the presence of radiologic and/or histopathologic changes consistent with usual interstitial pneumonia pattern on the current evaluation [11].
It is to be noted that the term “idiopathic” was removed from the older definition, as it was seen to be restrictive [11]. Making a distinction between idiopathic and non-idiopathic respiratory events is not easy as there are not well defined clinical or biological criteria [11]. So, although the acute deterioration could be due to an infectious etiology and it is not necessary to rule this out for the purpose of definition, at a practical level infection needs to be diagnosed and treated empirically or definitely as it does have a definite therapeutic recourse [11, 13]. It also follows from this that Broncho alveolar lavage (BAL) is not needed for diagnosis and hence it will help capture more of such events, but at the expense of specificity [11, 13]. BAL may not be needed when HRCT pattern is consistent with UIP, but when the Usual interstitial pneumonia (UIP) pattern is indeterminate or suspect then BAL can be useful [12]. Similarly, surgical lung biopsy (SLB) is recommended only when UIP is indeterminate or suspect [12]. However there is considerable morbidity and mortality associated with BAL or surgical biopsy in the context of AE and hence such procedures are to be generally avoided [11].
Similar to Acute lung injury in non-IPF lungs precipitated by triggers such as aspiration, post-operative, medication etc., exacerbation in IPF can be sub-categorized as either “triggered” when a known precipitating etiology is documented or “Idiopathic” when no such etiology is apparent [11].
The new definition also replaced the 30-day time restriction for the acute deterioration to “typically or generally of less than one-month duration” [11]. The phrase “typically less than 1 month” was included to provide precision but allow for the inclusion of exceptions that clinicians believe represent acute exacerbations [11]. A more flexible time interval may lead to “heterogeneity” among clinicians and clinical trial endpoint definitions for acute exacerbation [11].
The incidence of acute exacerbations is variably reported in literature. This is because exacerbations could be more common in certain populations like more elderly people who are also likely to have severe disease, inconsistent definitions and its use, statistical design, follow up time and other factors [2, 9]. Exacerbations are less common in mild to moderate disease compared to severe disease [3, 14]. Reporting can vary depending on the type of study as well. Prospective trials may lack sufficient data to report all exacerbations [2, 4, 8],typically include younger patients with less comorbidities, with mild to moderate disease and therefore may under report incidence [15]. Retrospective studies may over report depending on the criteria used, by including events with pulmonary embolism, heart failure etc. [2, 13, 16].
Suspected exacerbations, which may not satisfy the definition of definitive AE-IPF are also important as they are associated with poor outcomes [4].
A meta-analysis analyzed six trials and reported acute exacerbation rate of 41 acute exacerbations per 1000 patient/years [14]. Rate of acute exacerbations were much lower in trials that included only mild to moderate disease [14].
In a retrospective study from Korea, which included 461 patients with IPF of which 269 cases were biopsy-proven and the median follows up period was 22.9 months, acute exacerbation occurred in 96 (20.8%) patients, and 17 (17.7%) of those acute exacerbation patients experienced multiple episodes of acute exacerbations (range 2–3 episodes). The incidence of acute exacerbation was noted to be 14.2, 18.8 and 20.7 percent at the end of 1, 2 and 3 years respectively [17].
It is to be noted that exacerbation of IPF may even occur in individuals with limited fibrosis and well-preserved lung function [2]. In the STEP-IPF trail, definite AE-IPF was reported as 40 per 1000 patient-years. However, the combined definite and suspected AE-IPF increased the exacerbation rate to 200 per 1000 patient-year [2, 4, 8, 13].
There have been reports of increased rate of AE-IPF in people of Asian descent in the far east such as Japan and Korea, however this has not been proven by randomized control trials [7, 8, 18].
There are many risk factors for acute exacerbation. However, the most important risk factor is advanced disease [2, 14]. Other factors described in literature include low Forced vital capacity [8, 17], recent decline in FVC [19, 20], Low diffusion capacity for carbon monoxide [4], low 6 min walk test [4], pulmonary hypertension [21], poor baseline oxygenation [4, 22], increased dyspnea score [4], younger age group [2], presence of concurrent coronary artery disease [4], higher body mass index [22], previous history of acute exacerbation of IPF [19, 23].
Some important triggers for acute exacerbation have been described.
Infections are very common causes of respiratory deterioration. Exacerbations are more common in winter and spring season [24] and in those who are immunosuppressed [2, 25]. Postmortem analysis, multiplex polymerase chain reaction (PCR), pan viral micro array, high output cDNA sequencing and other techniques have demonstrated that infectious etiology is incriminated in many but not all acute exacerbations [23]. Based on the cumulative evidence which demonstrates infection to be causing some but not all acute exacerbations, it is thought to be an important but not exclusive trigger for precipitating acute exacerbations.
Aspiration of gastric contents has been postulated to be a causative factor for IPF and exacerbations in IPF.
In a case control study involving 24 acute exacerbations and 30 controls, Pepsin level in Broncho alveolar lavage (BAL) was found to be fairly commonly present, suggestive of gastric aspiration being fairly common in IPF.8 of the 24 acute exacerbation IPF patients had very high levels of Pepsin suggesting that aspiration of gastric contents could be a contributor for acute exacerbation [26].
In a study involving 32 patients with asymmetric idiopathic pulmonary fibrosis (AIPF) compared with 64 matched controls with symmetrical IPF, Gastro esophageal reflux disease (GERD) and AE-IPF was significantly higher in patients with AIPF with the left side being less commonly involved [27].
On the contrary, in a post hoc analysis of the two Phase III randomized placebo-controlled INPULSIS trials of Nintedanib in patients with IPF, the rate of decline of FVC in the placebo group was much higher in patients who were taking an antacid (Proton pump inhibitor or H2-receptor antagonists) at baseline when compared to those who were not [difference of − 47.5 mL/year (95% CI: −105.1, 10.1); p = 0.1057] [28].
The data as it is apparent, that although gastro esophageal reflex has been widely debated to be causative, is not very definitive. Therefore, it can be likely that the aspiration of gastro esophageal contents can trigger acute exacerbations like infections but is not the sole causative factor.
Many surgical procedures like bronchoscopy and BAL, lung biopsy, lung resection, non-thoracic surgery and others can precipitate acute exacerbation [24, 29, 30, 31, 32]. The mechanism of action is unclear but could be related to stress like volutrauma, barotrauma, free oxygen radicals, or intra operative fluid balance.
Air pollution can be a cause for interstitial lung disease. In a retrospective south Korean longitudinal cohort, out of 505 IPF patients 436 patients were included in the final analysis.75 patients experienced at least one exacerbation. There were 89 acute exacerbation events occurring over 1699 patient-years, for an incidence rate of 5.2 exacerbations per 100 patient-years. [23].
Air pollution data for each of the five pollutants Ozone (O3),Nitrogen di oxide (NO2), particles with a 50% cut-off aerodynamic diameter of <10 μm (PM10), sulfur dioxide (SO2) and carbon monoxide (CO) were measured prospectively at Tele-Monitoring-Systems (TMS) situated throughout Korea. Each TMS recorded hourly measurements of each pollutant during the study period. Mean and maximum exposures of all these 5 pollutants were recorded over the 42-day period prior to the exacerbation period. Acute exacerbation of IPF was significantly associated with important measurement metrics of O3 and NO2 during the exposure period. Mean Ozone and Nitrogen dioxide levels were weakly correlated; however, both were statistically significant independent predictors of AE-IPF [23].
Medications can provoke respiratory deterioration in interstitial pneumonia which closely resembles acute exacerbation. Such drugs include everolimus, interferon-gamma and others [33, 34]. Drugs and surgery used to treat Lung cancer patients with interstitial pneumonia did not appear to cause more exacerbations compared to best supportive care and hence should not be withheld when treating Lung cancer with interstitial pneumonia patients [35].
As noted, there have been many triggers associated with acute exacerbation of IPF. However currently the most accepted theory is that exacerbation is thought to be “an acceleration of the underlying inflammatory fibro proliferative disease process”.
This theory is supported by markers of cell injury as well as genetic expressions.
In one study by Collard et al., 47 patients with acute exacerbation of IPF, 20 patients with stable IPF and 20 patients with acute lung injury were studied. Plasma from these patients were collected and measured for biomarkers of cell activity/injury-receptor for advanced glycation end (RAGE) products, surfactant protein D, KL-6, von Willebrand factor; systemic inflammation-Interleukin-6; and biomarkers of coagulation/fibrinolysis-protein C, thrombomodulin, plasminogen activator inhibitor-1. Plasma from patients with AE-IPF showed higher levels of markers of type II alveolar epithelial cell injury/proliferation, endothelial cell injury, and coagulation/fibrinolysis very much like stable IPF but the response was much more exaggerated. This biomarker profile was different from patients with acute lung injury which was consistent with type I alveolar epithelial injury [36].
In another study, RNA was extracted from 23 stable IPF lungs, 8 IPF lungs with acute exacerbation of IPF and 15 control lungs. The gene expressions were studied. Results indicated that 579 genes were differentially expressed between stable IPF and acute exacerbation of IPF. Functional analysis of these genes was not suggestive of infectious or inflammatory etiology. Gene expression patterns in acute exacerbations of IPF and IPF samples were quite similar and different from the control lung arm [37].
Other immunological theories have also been proposed. Annexin 1 is an antigen found in human body which is increased in patients who have AE of IPF [38]. This antigen can induce both humoral and cell mediated immune responses and certain parts of this antigen have been implicated in the pathogenesis of AE of IPF [38]. Certain molecular studies have also been performed. Heat shock protein 47 (HSP47), has been studied and found to be a good bio marker for collagen production and secretion [39]. In studies comparing stable and AE-IPF patients, serum HSP47 were significantly elevated in AE-IPF patients in comparison to stable IPF patients [39]. Ironically patients who have anti-HSP70 autoantibodies in smaller studies have much poor prognosis due to AE of IPF when compared to controls or even those patients who have IPF but negative anti-HSP70 autoantibodies [40, 41].
Epithelial damage and impaired healing by abundance fibrosis has been an important theory that tries to explain the pathologic damage in IPF patients. When compared to IPF patients, patients with AE of IPF have higher bio markers of neutrophilic damage such as Alpha-defensins which are produced by activated neutrophils [37, 42] and also increased levels of Fibrocytes have been noted which have been found to be associated with worser outcomes in patients with AE of IPF [42, 43].
Patients present with worsening respiratory symptoms generally which are less than 30 days in duration. It consists of cough, worsening dyspnea especially on exertion, fever, malaise, and other flu like symptoms. Criteria for diagnosis include PaO2/FiO2 ratio < 225 or a decrease in PaO2 of ≥10 mmHg over time [8, 16].
Physical examination is consistent with IPF including bibasilar crackles on auscultation, but with increased respiratory rate [37].
Laboratory testing and imaging are directed to rule out other differentials like congestive heart failure, Myocardial infarction, pulmonary embolism, pulmonary hypertension, pulmonary infections etc. [2, 8]. Accordingly, complete blood count, B-type natriuretic peptide, C-reactive protein, chemistry profile including Blood urea nitrogen and serum creatinine can be performed along with highly sensitive troponins. Laboratory values are consistent with an infectious or inflammatory process but there is no evidence of infection on Blood culture, Urine antigen tests or Broncho alveolar lavage (BAL) if these tests are undertaken [8]. BAL if performed typically shows neutrophilic predominance [8]. BNP is typically elevated in heart failure and pulmonary hypertension [44]. Echo may be beneficial in heart failure and pulmonary hypertension [44]. CRP is typically elevated in infections and inflammation [44]. Pro calcitonin can guide when infection is suspected and even helping with limiting duration of antibiotic use [45]. D-dimer and CT pulmonary angiogram can help with ruling in or ruling out Pulmonary embolism [44].
High resolution computed tomography (HRCT) reveals bilateral ground glass or consolidative opacities superimposed on a background of typical HRCT features of IPF which includes bibasilar reticular opacities, honeycomb changes, and traction bronchiectasis [2].
Acute exacerbation of IPF is essentially a clinical diagnosis aided by predominantly noninvasive test. Although surgical biopsy can be performed for diagnosis which may show diffuse alveolar damage, the mortality and morbidity in the acute situation appear to be prohibitively high and not recommended [46].
Treatment is primarily supportive in nature.
Supplemental oxygen consisting of low flow and high flow oxygen can be used to keep Oxygen saturation (Spo2) more than 92%. Noninvasive ventilation mechanical ventilation (NIMV) and Mechanical ventilation (MV) is used as needed.
In a retrospective review of 19 hospitalized patients with IPF and AE, 1/3rd of patients had an infectious etiology, the percentage of patients who were discharged alive was 37% and only 14.8% of patients were alive at 1 year [47]. Patients with IPF experience AE very commonly. In IPF, about 40% of patients may die due to AE [48, 49]. In another observational study of 112 patients, 56 patients (42.9%) died due to AE [48]. The five-year survival rate of all patients with IPF was 38.3% and the Median survival time was 3.1 years post diagnosis. However, in patients who had an AE, the five-year survival rate was 10.7% and median survival time was 0.6 years [48].
In a pooled data consisting of nine studies, including 135 patients who were intubated for AE of IPF the cumulative mortality was 118 (87%) and short-term mortality (within 3 months of discharge) was 127 (94%) [50]. Therefore AE of IPF is not only common, but also a very poor predictor of survival. Based on these observations, the 2011 IPF guidelines discouraged MV in the vast majority and recommended its use in a selective minority of patients after careful weighing of risks and benefits [11]. However, this data pertains to a time period before 2007. In a study that reported US national data of 1703 patients who received Mechanical ventilation (MV)and 778 patients who received Noninvasive mechanical ventilation (NIMV),mortality was about 50% in those who received MV compared to 30% for those who received NIMV. The mortality of IPF patients treated with MV improved from 58.4% in 2006 to 49.3% in 2012 which was significant [51]. Overall this is suggestive that survival of patients treated with MV has seen a marginal improvement which could be due to various factors such as relative changes in diagnostic criteria and their use, difference in variables used and study design, differences in the severity of disease (patients with decreased FVC have poorer prognosis), judicious selection of patients who were placed on MV and widespread adoption and use of lung protective ventilation strategies [52]. Hence it is imperative that well informed discussions relating to advance care directives are made at the time of diagnosis and re visited when hospitalized [50]. In patients who are candidates for Lung transplant, the use of mechanical ventilation and extra corporeal membrane oxygenation, can be effective and lifesaving [11, 52, 53, 54, 55].
Ventilator induced lung injury (VILI) secondary to use of MV results in lung damage and poor prognosis [52]. In IPF, the lungs are fibrotic and non-compliant. Lower PEEP may be more beneficial and protective along with low tidal volume ventilation, hence minimizing both volutrauma and barotrauma [52, 56]. NIMV and high flow oxygen are being increasingly used and may be beneficial [56, 57]. Both NIMV and High flow Oxygen could be beneficial in patients who are not appropriate or choose to forego intubation, the survival may be the same with both modalities [57, 58],with high flow nasal oxygen being better tolerated, allowing patients to even eat and drink [57, 58, 59]. Hence they could be very effective means for palliative care [57, 58].
In patients who undergo thoracic surgery, VILI may be a potential etiological mechanism and can be minimized by the aforementioned lung protective ventilation including reducing lung volume, low PEEP, low partial pressure of inspired oxygen (Fio2), and less invasive surgical techniques [52, 56, 60, 61].
Symptoms such as dyspnea are treated with a palliative intent [8, 11]. Oxygen and opioids can also be given for symptom control [8, 11].
In IPF, a combination of inflammation, epithelial cell injury, fibro proliferative repair, and tissue remodeling which interact with the coagulation system help characterize IPF as a procoagulant state [62]. The use of therapeutic anticoagulation such as Warfarin or Alfa-Thrombomodulin has proven to be either harmful or non-beneficial in well conducted studies [63, 64, 65]. There is no evidence supporting therapeutic anticoagulation in patients experiencing acute exacerbation [63]. Nevertheless, patients with IPF have almost twice the risk of venous thromboembolism compared to general population and hence pharmacological venous thromboprophylaxis should be routinely used in hospitalized patients [66, 67].
There is not enough evidence of protective role from the use of antacids, but patients who are already using them can continue with their use [68, 69]. Evidence is often contradictory if antacids protect or may potentiate or worsen AE of IPF [70, 71].
Corticosteroids have been used extensively but the practice is driven by expert opinion and anecdotal reports and not driven by good data. Expert guidelines give a weak recommendation to the use of steroids [2, 6]. Acute IPF is characterized by high degree of inflammation with areas of diffuse alveolar damage secondary to Acute Lung injury and organizing pneumonia [9]. Therefore, the use of high dose steroids is intuitively thought to be beneficial [9, 72, 73, 74], in spite of absence of good data from randomized control trials [9]. Dosage and duration are also not well defined in literature, although it is typical to use initially high dose corticosteroids followed by a rapid tapering course, as longer duration of steroids may be harmful in IPF [9, 62]. In EXAFIP, a randomized control trial comparing Cyclophosphamide with corticosteroids against placebo with corticosteroids in AE of IPF, the steroid regimen used in all patients was Methylprednisolone 10 mg/kg per day for 3 days followed by a progressive taper to 10 mg per day for patients above 65 kg and 7·5 mg per day for patients below 65 kg at the end of 6 months [75]. Similarly in a RCT involving 77 patients in Japan, Alpha-Thrombomodulin (ART-123) was compared against placebo. All patients received glucocorticoids in two courses of pulse Methylprednisolone (500–1000 mg/day) for 3 days followed by Prednisolone 0.5–1.0 mg/kg/day for 4 days followed by gradual taper [64]. Smaller retrospective studies have shown that using high dose of glucocorticoids used in first 30 days prevent recurrence of exacerbation when compared to lower doses in the same duration or after 30 days but this has not been substantiated by other studies [76, 77]. The use of high dose steroids has been noted to increase survival in non-IPF exacerbation of Interstitial lung disease [76]. It is noteworthy that some studies and even guidelines recommend using no immunosuppressives in select patients, as mortality was no better in the immunosuppressed group when compared to the non-immunosuppressed, with higher incidence of infection in the immune suppressed group, especially in severe disease [11, 14].
Concomitant Immunosuppressive therapy with steroids have also been used and the evidence base for this practice is also not very sound [2, 48]. While treatments such as Alfa-Thrombomodulin and Cyclophosphamide along with concomitant glucocorticoids have been subjected to randomized control trials and have not been shown to improve outcomes [64, 75], others do not have much evidence as they were too small, were uncontrolled, used historical data as control or had no control arm [2]. The latter studies have used medications like Tacrolimus, Cyclosporin-A, Rituximab combined with plasma exchange, Intravenous Immunoglobulin, and polymyxin B-immobilized fiber column (PMX) [6]. Other medications that have been used include Acetylcysteine as standalone therapy, sildenafil, bosentan, interferon-gamma 1b, warfarin, ambrisentan, and imatinib [8].
In a small retrospective study consisting of 11 patients in each group, Corticosteroids alone were compared with Cyclosporin-A and Corticosteroids. The mortality was similar in each group but the Cyclosporin-A group appeared to have longer survival [78]. However in a larger retrospective review with 384 patients in Cyclosporin-A and high dose Corticosteroids and 7605 patients treated with high dose Corticosteroids alone in Japan, no change in survival was noted [79].
Other considerations include empiric treatment of a course of antibiotics since infectious etiology can be treated but cannot be ruled out conclusively in the vast majority of cases [2]. Procalcitonin has been used in clinical trials and can reduce the duration of antibiotics (8.7 ± 6.6 compared to 14.2 ± 5.2 days in the routine treatment group), without any effect on treatment success, mortality rate, days of hospitalization and ventilation therapy [45]. Tacrolimus, an immunosuppressive drug used widely in solid organ transplant patients including Lung transplant was found to have beneficial survival effects and protection against future exacerbations in small retrospective studies, with lack of data from better designed controlled studies [80]. Direct hemoperfusion with Polymyxin B immobilized fiber column (PMX-DHP) has been used in AE of IPF to absorb endotoxins and reactive oxygen species, among other toxic substances, as well as selectively remove activated neutrophils and preventing activation of monocytes with a goal to limit endothelial damage [81, 82]. PMX-DHP may act by adsorbing harmful cytokines such as vascular endothelial growth factor and may have anti-fibrotic effect [83, 84]. The adsorption of proinflammatory, profibrotic and proangiogenic cytokines is postulated to be an important mechanistic action of PMX-DHP [83]. The use of PMX-DHP along with Corticosteroids has demonstrated improvement in oxygenation, with possible improvement in survival in a multicentric Japanese retrospective study with 73 patient who had AE of IPF [82]. There is a prevailing hypothesis that auto antibodies may have a role in IPF progression. Removal of these auto antibodies by plasma exchange and Rituximab followed by IVIG subsequently may be beneficial in AE-IPF [62, 85]. A small pilot study involving 11 patients has shown the safety and possible efficacy, paving way for a Phase 3 randomized control trial [85].
Interestingly in a retrospective study, patients who were not on any immunosuppression had better survival than those who were on immunosuppression [5].
There has been considerable interest in developing prognostication scores for AE of IPF. A number of markers have been used in different studies and Forced vital capacity %, Diffusion capacity for Carbon monoxide, Pao2/Fio2 (P/F) ratio, HRCT patterns, Acute Physiology and Chronic Health Evaluation II score (APACHE II), Glasgow prognostic score and serum biomarkers like C-reactive protein (CRP), Krebs von den Lungen-6 (KL-6) have all been considered [86]. In a retrospective study of 108 patients, a lower FVC % at baseline (1 year before AE) and P/F ratio on AE presentation were predictive of mortality [86]. In another study of 103 AE-IPF cases, a combination of P/F ratio less than 250 (P), CRP ≥ 5.5 (C), and diffuse HRCT pattern (radiological) (R), together called as PCR index was used to stratify and predict mortality at the end of 3 months [87]. In a systematic review and meta-analysis, 37 studies and 31 prognostic factors were analyzed [88]. Five independent variables after multivariate analysis were found to be helpful with prognostication namely APACHE II score, P/F ratio, LDH level, white blood cell (WBC) count, and oxygen therapy before AE [88]. Interestingly the latter did not find use of FVC or imaging scores to be helpful in terms of prognostication [88]. Prognostication scores and models are certainly good research tools but not commonly used in clinical practise as no intervention other than good supportive care has been found to be useful.
Prevention of exacerbation in IPF is the most effective strategy as we do not seem to have very effective therapies once the exacerbation gets underway. Avoidance of air pollutants [23], preventing infections like Streptococcal pneumonia and Influenza by vaccination [26, 61], general hygiene measures like handwashing again to prevent infections [52], and judicious use of antacids may be helpful strategies [68, 69].
Many medications have been tested, using prevention of acute exacerbation as an end point. Acetylcysteine monotherapy, bosentan, interferon-gamma,sildenafil, showed no effect [8]. Others like imatinib, ambrisentan, triple therapy (prednisone, azathioprine, acetylcysteine combination) and warfarin showed increased risk of exacerbation [8].
Azuma et al. studied 107 IPF patients in a phase 2 Randomized placebo-controlled trial comparing Pirfenidone and placebo. Although there were no acute exacerbations noted in the Pirfenidone arm compared to placebo [89], the same results could not be reproduced in a phase 3 RCT with 275 patients, showing no difference between the intervention and control arm [18]. In the large phase 3 RCT’s, CAPACITY and ASCEND which compared Pirfenidone with placebo yet again, unfortunately AE of IPF as an end point was not studied [90, 91]. Nevertheless, a pooled analysis of the CAPACITY and ASCEND trial did reveal a reduction in non-elective respiratory related hospitalization favoring Pirfenidone [92]. Interestingly Pirfenidone in small studies has proven to be safe and effective in preventing exacerbations in peri operative period in patients who were given 2–4 weeks of medication prior to surgery and continued post operatively when compared against historical controls [93, 94]. Larger RCTs need to be performed for this promising intervention [94].
Another antifibrotic agent Nintedanib was studied after Pirfenidone, which showed a favorable effect against placebo for preventing AE of IPF in the phase 2 TOMORROW trial and phase 3 INPULSIS-2 trial, but no such effect was seen in the phase 3 INPULSIS-1 trial [95, 96]. However the pooled analysis of patients from TOMORROW and INPULSIS trials [6],consisting of 1231 patients (Nintedanib n = 723, placebo n = 508), the hazard ratio for time to first acute exacerbation was 0.53 (95% CI: 0.34, 0.83; p = 0.0047) favoring Nintedanib. The proportion of patients with ≥1 acute exacerbation was 4.6% in the Nintedanib group and 8.7% in the placebo group [6]. Nintedanib can be added after recovering from an exacerbation or continued if it was previously being used.
In a systematic review and meta-analysis, 12,956 patients were included comparing the use of anti fibrotics (Pirfenidone or Nintedanib) vs. nonuse of antifibrotics, which showed that the use of antifibrotics decreased all-cause mortality, RR 0.55 (95% CI, 0.45–0.66). The same review included seven studies involving 2002 treated and 1323 non-treated patients, and showed a decrease in AE, which was statistically significant for Nintedanib (RR 0.62 [95% CI, 0.43–0.89) but only non-significant decrease for Pirfenidone, RR of 0.57 (95% CI, 0.29–1.12) [1].
Overall, the evidence favors Nintedanib over Pirfenidone in terms of preventing AE of IPF. However, there are no head to head comparisons between these two approved medications and real world data could produce results to the contrary [97]. Hence it would be prudent to plan design and conduct appropriate RCT that would give an unambiguous answer to this very important question.
Episodes of Acute exacerbation are important events in the disease course of IPF. Up to 40% of deaths in IPF are caused by acute exacerbations. After the initial diagnosis, the median survival of patients with acute exacerbation was much shorter (15.5 months) than that of patients without respiratory deterioration (60.6 months). The 5 year rate of survival of patients with acute exacerbation was 18.4%, whereas 50.0% of patients without respiratory deterioration survived.
While medications like Nintedanib can slow down progression of disease and prevent exacerbations, once diagnosed it has no known effective treatment. Hence more research is needed to alter the disease course of IPF as well as prevent the occurrence of these exacerbations which invariably is an indicator of poor prognosis.
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Among these heavy metals, a few have direct or indirect impact on the human body. Some of these heavy metals such as copper, cobalt, iron, nickel, magnesium, molybdenum, chromium, selenium, manganese and zinc have functional roles which are essential for various diverse physiological and biochemical activities in the body. However, some of these heavy metals in high doses can be harmful to the body while others such as cadmium, mercury, lead, chromium, silver, and arsenic in minute quantities have delirious effects in the body causing acute and chronic toxicities in humans. The focus of this chapter is to describe the various mechanism of intoxication of some selected heavy metals in humans along with their health effects. Therefore it aims to highlight on biochemical mechanisms of heavy metal intoxication which involves binding to proteins and enzymes, altering their activity and causing damage. More so, the mechanism by which heavy metals cause neurotoxicity, generate free radical which promotes oxidative stress damaging lipids, proteins and DNA molecules and how these free radicals propagate carcinogenesis are discussed. Alongside these mechanisms, the noxious health effects of these heavy metals are discussed.",book:{id:"7111",slug:"poisoning-in-the-modern-world-new-tricks-for-an-old-dog-",title:"Poisoning in the Modern World",fullTitle:"Poisoning in the Modern World - New Tricks for an Old Dog?"},signatures:"Godwill Azeh Engwa, Paschaline Udoka Ferdinand, Friday Nweke Nwalo and Marian N. Unachukwu",authors:[{id:"241837",title:"Mr.",name:"Godwill Azeh",middleName:null,surname:"Engwa",slug:"godwill-azeh-engwa",fullName:"Godwill Azeh Engwa"},{id:"274194",title:"BSc.",name:"Paschaline Ferdinand",middleName:null,surname:"Okeke",slug:"paschaline-ferdinand-okeke",fullName:"Paschaline Ferdinand Okeke"},{id:"286975",title:"Dr.",name:"Friday",middleName:null,surname:"Nweke Nwalo",slug:"friday-nweke-nwalo",fullName:"Friday Nweke Nwalo"},{id:"286976",title:"Dr.",name:"Marian",middleName:null,surname:"Unachukwu",slug:"marian-unachukwu",fullName:"Marian Unachukwu"}]},{id:"49459",title:"Pharmacokinetics of Drugs Following IV Bolus, IV Infusion, and Oral Administration",slug:"pharmacokinetics-of-drugs-following-iv-bolus-iv-infusion-and-oral-administration",totalDownloads:15480,totalCrossrefCites:16,totalDimensionsCites:24,abstract:null,book:{id:"4491",slug:"basic-pharmacokinetic-concepts-and-some-clinical-applications",title:"Basic Pharmacokinetic Concepts and Some Clinical Applications",fullTitle:"Basic Pharmacokinetic Concepts and Some Clinical Applications"},signatures:"Tarek A. Ahmed",authors:[{id:"175649",title:"Dr.",name:"Tarek A",middleName:null,surname:"Ahmed",slug:"tarek-a-ahmed",fullName:"Tarek A Ahmed"}]},{id:"29240",title:"Oral Absorption, Intestinal Metabolism and Human Oral Bioavailability",slug:"oral-absorption-intestinal-metabolism-and-human-oral-bioavailability-",totalDownloads:27175,totalCrossrefCites:28,totalDimensionsCites:58,abstract:null,book:{id:"672",slug:"topics-on-drug-metabolism",title:"Topics on Drug Metabolism",fullTitle:"Topics on Drug Metabolism"},signatures:"Ayman El-Kattan and Manthena Varma",authors:[{id:"85539",title:"Dr.",name:"Ayman",middleName:null,surname:"El-Kattan",slug:"ayman-el-kattan",fullName:"Ayman El-Kattan"},{id:"88221",title:"Dr.",name:"Manthena",middleName:null,surname:"Varma",slug:"manthena-varma",fullName:"Manthena Varma"}]},{id:"66259",title:"Antioxidant Compounds and Their Antioxidant Mechanism",slug:"antioxidant-compounds-and-their-antioxidant-mechanism",totalDownloads:7587,totalCrossrefCites:58,totalDimensionsCites:152,abstract:"An antioxidant is a substance that at low concentrations delays or prevents oxidation of a substrate. Antioxidant compounds act through several chemical mechanisms: hydrogen atom transfer (HAT), single electron transfer (SET), and the ability to chelate transition metals. The importance of antioxidant mechanisms is to understand the biological meaning of antioxidants, their possible uses, their production by organic synthesis or biotechnological methods, or for the standardization of the determination of antioxidant activity. In general, antioxidant molecules can react either by multiple mechanisms or by a predominant mechanism. The chemical structure of the antioxidant substance allows understanding of the antioxidant reaction mechanism. This chapter reviews the in vitro antioxidant reaction mechanisms of organic compounds polyphenols, carotenoids, and vitamins C against free radicals (FR) and prooxidant compounds under diverse conditions, as well as the most commonly used methods to evaluate the antioxidant activity of these compounds according to the mechanism involved in the reaction with free radicals and the methods of in vitro antioxidant evaluation that are used frequently depending on the reaction mechanism of the antioxidant.",book:{id:"8008",slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Norma Francenia Santos-Sánchez, Raúl Salas-Coronado, Claudia Villanueva-Cañongo and Beatriz Hernández-Carlos",authors:[{id:"143354",title:"Dr.",name:"Raúl",middleName:null,surname:"Salas-Coronado",slug:"raul-salas-coronado",fullName:"Raúl Salas-Coronado"},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez"},{id:"193718",title:"Dr.",name:"Beatriz",middleName:null,surname:"Hernández-Carlos",slug:"beatriz-hernandez-carlos",fullName:"Beatriz Hernández-Carlos"},{id:"278133",title:"Dr.",name:"Claudia",middleName:null,surname:"Villanueva-Cañongo",slug:"claudia-villanueva-canongo",fullName:"Claudia Villanueva-Cañongo"}]},{id:"66742",title:"Introductory Chapter: Alkaloids - Their Importance in Nature and for Human Life",slug:"introductory-chapter-alkaloids-their-importance-in-nature-and-for-human-life",totalDownloads:4130,totalCrossrefCites:16,totalDimensionsCites:32,abstract:null,book:{id:"6828",slug:"alkaloids-their-importance-in-nature-and-human-life",title:"Alkaloids",fullTitle:"Alkaloids - Their Importance in Nature and Human Life"},signatures:"Joanna Kurek",authors:[{id:"214632",title:"Dr.",name:"Joanna",middleName:null,surname:"Kurek",slug:"joanna-kurek",fullName:"Joanna Kurek"}]}],onlineFirstChaptersFilter:{topicId:"19",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"83076",title:"Treatments for the Infection by SARS-CoV-2",slug:"treatments-for-the-infection-by-sars-cov-2",totalDownloads:7,totalDimensionsCites:0,doi:"10.5772/intechopen.106232",abstract:"In late 2019, pneumonia cases from unknown origin were detected in Wuhan, China. The cause was a new coronavirus. The World Health Organization (WHO) named the virus SARS-CoV-2 and COVID-19 the associated disease. In the first months of 2020, this disease became a pandemic with a high lethality reported. Since then, the search for treatments began. We started by searching among treatments previously approved for human use that were not designed for COVID-19 and were considered to treat this condition. We continued searching on the therapeutics guidelines published by the WHO for the management of infection by SARS-CoV-2. Based on these results, we searched for the literature in PubMed to obtain further evidence on the drugs against SARS-CoV-2. The treatments presented in this chapter are Ivermectin, Hydroxychloroquine, Nitazoxanide, Azithromycin, Molnupiravir, Casirivimab-Imdevimab, Ritonavir-Nirmatrelvir, Ritonavir-Lopinavir, Remdesivir, and Favipiravir. Two years ahead of the start of the COVID-19 pandemic, a plenty of options for treatment have been investigated. Only a few of them have been shown to be efficient and safe. According to the WHO, Ritonavir-Nirmatrelvir outperforms other proposed therapeutics.",book:{id:"11690",title:"COVID-19 Drug Development - Recent Advances, New Perspectives, and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11690.jpg"},signatures:"Nicolás Padilla-Raygoza, Gilberto Flores-Vargas, María de Jesús Gallardo-Luna, Efraín Navarro-Olivos, Francisco Javier Magos-Vázquez and Daniel Alberto Díaz-Martínez"},{id:"83054",title:"Pulsatory Liposome: A Possible Biotechnological Device",slug:"pulsatory-liposome-a-possible-biotechnological-device",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.106347",abstract:"A unilamellar liposome filled with an osmotic solution is introduced into a hypotonic aqueous environment. Because of the mechanical tension induced by the osmotic flow, the vesicle swells up to a critical size, when suddenly a transbilayer pore appears and the vesicle relaxing stage starts. A part of the intracellular material leaks out through this pore, and the liposome membrane relaxes and finally recovers. The swelling begins again and the liposome experiences a periodical process. For this reason, we have named it a pulsatory liposome. The swelling of the liposome is described by a differential equation. All the processes which contribute to the vesicle relaxing and its coming back to the initial size are described by three differential equations. The pulsatory liposome can be programmed to work a number of cycles, established before. The activity of a pulsatory liposome can be characterized by the following parameters: (a) number of cycles, the length time of each cycle, and liposome activity life; (b) the length time of the swelling stage and the relaxation stage for each cycle; (c) the amount of solute leaked out through the pore in each cycle. The pulsatory liposome may be regarded as a two-stroke engine.",book:{id:"11814",title:"Liposomes - Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11814.jpg"},signatures:"Dumitru Popescu and Alin Gabriel Popescu"},{id:"82962",title:"Pluralism Medical Treatment, Prevention, and Control of COVID-19 Infection and Its Long-Sufferings among the Older Adults in the Northeast of Thailand from 2019 to 2022",slug:"pluralism-medical-treatment-prevention-and-control-of-covid-19-infection-and-its-long-sufferings-amo",totalDownloads:51,totalDimensionsCites:0,doi:"10.5772/intechopen.106339",abstract:"COVID-19 in 2019 has brought both changes and challenges to the world. This global pandemic has an impact on people of all age levels, especially older adults. In Thailand, older persons are at high risk of COVID-19 infection. They are included in the so-called 608 groups. The objective of this review article was to synthesize and present medical pluralism, the development of drugs from herbs, and projects conducted to treat, prevent, and control the infection and long sufferings of COVID-19. The review covers 10 studies, three projects produced at Mahasarakham University, Chaiyaphum Rajabhat University, and Khon Kaen University that were reviewed, synthesized, and analyzed. The results of the synthesis indicate that modern and Thai traditional medicine can help reduce the severity of the infection and long sufferings of COVID-19. The medical pluralism between modern and Thai traditional medicine is needed to remedy COVID-19 cases among the older adults in the Northeast of Thailand.",book:{id:"11690",title:"COVID-19 Drug Development - Recent Advances, New Perspectives, and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11690.jpg"},signatures:"Pissamai Homchampa, Khemika Napattaradechanon, Parichat Yatniyom, Thawalrat Ratanasiri, Piyaporn Sansila, Thanawan Sirisuk, Thawalwong Ratanasiri and Amornrat Ratanasiri"},{id:"82353",title:"Pharmacovigilance of Biological Drugs",slug:"pharmacovigilance-of-biological-drugs",totalDownloads:8,totalDimensionsCites:0,doi:"10.5772/intechopen.105520",abstract:"The use of biological drugs has significantly increased over the past decades and has allowed for the treatment of many life-threatening and chronic diseases. The patent expiration of biological innovative medicines enables copies of these drugs called biosimilars. The availability of biosimilars enhances competition, with the potential to improve patient access to biological medications and contribute to the financial sustainability of the healthcare systems. Unlike equivalent drugs, biosimilars are not identical but similar to their innovator products because of the differences in the manufacturing process, which is a biological process. However, they are considered comparable to their originators in safety, quality characteristics, biological activity, and efficacy. The regulatory procedures used for generic drugs cannot be applied for biosimilars, so they are subjected to rigorous characterization as well as comparative clinical studies. Since they are highly complex molecules produced from living cells, even small change in the production process can have major implications on their safety and effectiveness profile, causing a potential risk of immune-based adverse reactions. For all these reasons, for biological drugs, a robust long-term pharmacovigilance system is necessary. It is desirable that in the future, there are further guidance and resolution of the ongoing discussions on biosimilar labeling, naming, pharmacovigilance and interchangeability/substitution, to ensure the appropriate use of these drugs in clinical practice.",book:{id:"11679",title:"Pharmacovigilance and Regulations",coverURL:"https://cdn.intechopen.com/books/images_new/11679.jpg"},signatures:"Simona Guerzoni, Flavia Lo Castro, Carlo Baraldi, Giuliana Colella and Luca Pani"},{id:"82868",title:"Recent Strategies for Ocular Drug Delivery: Promises and Challenges",slug:"recent-strategies-for-ocular-drug-delivery-promises-and-challenges",totalDownloads:9,totalDimensionsCites:0,doi:"10.5772/intechopen.106335",abstract:"Ocular diseases include various anterior and posterior segment diseases. Due to the unique anatomy and physiology of the eye, efficient ocular drug delivery is a great challenge to researchers. The emerging nanoscience is playing an important role in the development of novel strategies for ocular disease management. Various active molecules have been designed to associate with nanocarriers to overcome ocular barriers and interact with certain ocular tissues. In this chapter, highlights will be made on barrier to intraocular delivery, general pathways for ocular absorption, and factors affecting intraocular bioavailability. The recent attempts of nanotechnology for treating anterior and posterior ocular diseases will be explored. This will include nanomicelles, nanoparticles, nanosuspensions, vesicular systems, in situ gel, dendrimers, contact lenses, implants, microneedles, and cell-based delivery systems. In addition, gene-based ocular delivery systems will be discussed. In this chapter, we will also provide a comprehensive overview of drug-device combinations used for ocular diseases such as glaucoma, dry eye disease, infections, and inflammations. Furthermore, drug delivery devices for ocular surgeries are discussed. Finally, challenges and future prospective of ocular delivery systems will be explored.",book:{id:"11688",title:"Advances in Drug Delivery Methods",coverURL:"https://cdn.intechopen.com/books/images_new/11688.jpg"},signatures:"Amal H. El-Kamel and Asmaa A. Ashour"},{id:"82727",title:"Mesoporous Silica Based Cancer Theranostic: A Modern Approach in Upcoming Medicine",slug:"mesoporous-silica-based-cancer-theranostic-a-modern-approach-in-upcoming-medicine",totalDownloads:15,totalDimensionsCites:0,doi:"10.5772/intechopen.105447",abstract:"In case cancers are located deep inside the body and are very tough to diagnose, diagnostic tools like MRI/CT scans can be employed to detect these cancers. The major challenge in such cases is the delivery of MRI active agents or visualizing agents to the target site. In this context we will discuss different mesoporous nanoparticles that can be employed to target the tissue at a specific location, its functionalization to reach the target site (Folic acid), different simple dyes as well as specific dyes which offer theranostic functionality. The nanoparticles like mesoporous silica nanoparticles offer the possibility to load therapeutic and diagnostic agents. Its surface allow multiple functionalization and conjugations which offer target specific delivery of these agents. Moreover we will also overview different modern drug delivery inventions for offering theranostic application.",book:{id:"11688",title:"Advances in Drug Delivery Methods",coverURL:"https://cdn.intechopen.com/books/images_new/11688.jpg"},signatures:"Ajinkya Pote, Vikas Ahirrao and Vishal Pande"}],onlineFirstChaptersTotal:54},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:11,numberOfPublishedChapters:91,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:333,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:11,numberOfPublishedChapters:143,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:124,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:23,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188",scope:"This series will provide a comprehensive overview of recent research trends in various Infectious Diseases (as per the most recent Baltimore classification). Topics will include general overviews of infections, immunopathology, diagnosis, treatment, epidemiology, etiology, and current clinical recommendations for managing infectious diseases. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This book series will focus on various aspects and properties of infectious diseases whose deep understanding is essential for safeguarding the human race from losing resources and economies due to pathogens.",coverUrl:"https://cdn.intechopen.com/series/covers/6.jpg",latestPublicationDate:"August 16th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:13,editor:{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"3",title:"Bacterial Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/3.jpg",isOpenForSubmission:!0,editor:{id:"205604",title:"Dr.",name:"Tomas",middleName:null,surname:"Jarzembowski",slug:"tomas-jarzembowski",fullName:"Tomas Jarzembowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKriQAG/Profile_Picture_2022-06-16T11:01:31.jpg",biography:"Tomasz Jarzembowski was born in 1968 in Gdansk, Poland. He obtained his Ph.D. degree in 2000 from the Medical University of Gdańsk (UG). After specialization in clinical microbiology in 2003, he started studying biofilm formation and antibiotic resistance at the single-cell level. In 2015, he obtained his D.Sc. degree. His later study in cooperation with experts in nephrology and immunology resulted in the designation of the new diagnostic method of UTI, patented in 2017. He is currently working at the Department of Microbiology, Medical University of Gdańsk (GUMed), Poland. Since many years, he is a member of steering committee of Gdańsk branch of Polish Society of Microbiologists, a member of ESCMID. He is also a reviewer and a member of editorial boards of a number of international journals.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorTwo:{id:"484980",title:"Dr.",name:"Katarzyna",middleName:null,surname:"Garbacz",slug:"katarzyna-garbacz",fullName:"Katarzyna Garbacz",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003St8TAQAZ/Profile_Picture_2022-07-07T09:45:16.jpg",biography:"Katarzyna Maria Garbacz, MD, is an Associate Professor at the Medical University of Gdańsk, Poland and she is head of the Department of Oral Microbiology of the Medical University of Gdańsk. She has published more than 50 scientific publications in peer-reviewed journals. She has been a project leader funded by the National Science Centre of Poland. Prof. Garbacz is a microbiologist working on applied and fundamental questions in microbial epidemiology and pathogenesis. Her research interest is in antibiotic resistance, host-pathogen interaction, and therapeutics development for staphylococcal pathogens, mainly Staphylococcus aureus, which causes hospital-acquired infections. Currently, her research is mostly focused on the study of oral pathogens, particularly Staphylococcus spp.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorThree:null},{id:"4",title:"Fungal Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",isOpenForSubmission:!0,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null},{id:"5",title:"Parasitic Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",isOpenForSubmission:!0,editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. 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He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:null,institution:null},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"417317",title:"Mrs.",name:"Chiedza",middleName:null,surname:"Elvina Mashiri",slug:"chiedza-elvina-mashiri",fullName:"Chiedza Elvina Mashiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"352140",title:"Dr.",name:"Edina",middleName:null,surname:"Chandiwana",slug:"edina-chandiwana",fullName:"Edina Chandiwana",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"342259",title:"B.Sc.",name:"Leonard",middleName:null,surname:"Mushunje",slug:"leonard-mushunje",fullName:"Leonard Mushunje",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"347042",title:"Mr.",name:"Maxwell",middleName:null,surname:"Mashasha",slug:"maxwell-mashasha",fullName:"Maxwell Mashasha",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"2941",title:"Dr.",name:"Alberto J.",middleName:"Jorge",surname:"Rosales-Silva",slug:"alberto-j.-rosales-silva",fullName:"Alberto J. Rosales-Silva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"437913",title:"Dr.",name:"Guillermo",middleName:null,surname:"Urriolagoitia-Sosa",slug:"guillermo-urriolagoitia-sosa",fullName:"Guillermo Urriolagoitia-Sosa",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"435126",title:"Prof.",name:"Joaquim",middleName:null,surname:"José de Castro Ferreira",slug:"joaquim-jose-de-castro-ferreira",fullName:"Joaquim José de Castro Ferreira",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Aveiro",country:{name:"Portugal"}}},{id:"437899",title:"MSc.",name:"Miguel Angel",middleName:null,surname:"Ángel Castillo-Martínez",slug:"miguel-angel-angel-castillo-martinez",fullName:"Miguel Angel Ángel Castillo-Martínez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"289955",title:"Dr.",name:"Raja",middleName:null,surname:"Kishor Duggirala",slug:"raja-kishor-duggirala",fullName:"Raja Kishor Duggirala",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jawaharlal Nehru Technological University, Hyderabad",country:{name:"India"}}}]}},subseries:{item:{id:"8",type:"subseries",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11404,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. 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