**3.1. CAP: epidemiology**

Community-acquired pneumonia (CAP) is still the leading cause of death attributable to infectious diseases, and epidemiological data show that its attributable mortality rate remains static or is rising, while declining for cardiovascular diseases and many cancers in developed countries [40]. Mortality in European adults varies from country to country and based on the age, it ranges from 4.5 to 5 per 100,000 in turkey and Georgia to 30 to 35 per 100,000 in Portugal and UK [41]. Near a half of under-five deaths worldwide are due to preventable diseases including pneumonia, diarrhea, and malaria with 2.2 million deaths in children under 5 years in 2012, in Nigeria, Democratic Republic of Congo, India, Pakistan, and China [42]. The overall prevalence of CAP in Africa is unknown, due to the lack of standardized protocols and reporting. A study in Uganda reported *Klebsiella pneumoniae* as the prevalent pathogen in neonates and *S. pneumoniae* was the most common etiological agent in those aged between 3 months and 5 years [43–45].

Outcome of pneumonia is still a health concern, mainly in developing countries, despite the development of new antibacterial agents. This phenomenon relays on the emerging antibiotic resistance of the pathogen on one hand and on host-related factors (impaired immunity, poor hygiene, age, malnutrition, comorbidities) on the other. Innovative approaches through better understanding of pathophysiology of the disease and environmental changes, early diagnosis techniques, multidisciplinary approach, and host-driven measures (behavior, accessibility to health facilities) need to be developed to improve the control of respiratory mortality.

Community-acquired pneumonias is the leading cause of death due to the infectious disease in both developed and developing world [22]. Developing countries are also the most affected due to many additional conditions such as poverty, low economic access to healthcare, lack of appropriate tools for early diagnosis, many socio-cultural barriers, and the unpreparedness against environmental changes. A study from Tanzania has identified the negative role of difficult diagnoses and comorbidities in the prognosis of CAP [46]. Children under 5 years and elderly are the most vulnerable population, and 30-day mortality has not been improved since the 1950s, despite the availability of new antibiotics [47]. CAP occurs in almost 1–10 per 1000 of the adult population each year and more commonly in extreme ages. According to the WHO European region report in 2010, lower respiratory tract infections ranked fifth in the global burden disease study [30]. The same report identified infectious diseases, childhood illnesses, and maternal causes of death as accounting for 70% of the burden of diseases in sub-Saharan Africa, while representing <20% in all others countries. Even reduced compared to two decades ago, the rate of mortality caused by diarrheal and low tract infection diseases remains high and the major cause of early deaths in the country. The big five, COPD, asthma, low respiratory tract infections, TB, and lung cancer are among the most common causes of severe illness death worldwide.

The lack of standardized protocols and regular statistic reports does not allow the assessment of accurate incidence rate of CAP across the sub-Saharan region. In Europe, this incidence rate in adults is between 1.07 and 1.2 per 1000 person year and 1.54 and 1.7 per 1000 population according to a report by Torres et al. [48]. Older age and underlying comorbidities including COPD, cardiovascular and liver diseases, diabetes, cancers as well as all causes of immunosuppression (steroids treatment, malnutrition, HIV-AIDS) affect the prognosis of the disease and this is highlighted by the CURB 65 criteria in use for assessing the severity of CAP. There is a regular increase in the incidence of CAP worldwide, may be associated to demographic changes, increasingly aging population, growing poverty, low accessibility to healthcare facilities, precarity and war displacements, smoking and alcohol consumption. It is more and more clear that air pollution and climate change play important roles in the rising morbidity and mortality related to respiratory diseases. The heat stress linked to the warming of the climate induces environmental changes allowing the emergence of new pathogens worldwide. The real involvement of these ecological modifications needs to be addressed.

#### **3.2. Pathophysiology**

and the air pollutants. Green spaces are shown to block secondary air pollutants (ozone and PM 2.5). Rationale management of green structures needs to be encouraged in the urbaniza-

Community-acquired pneumonia (CAP) is still the leading cause of death attributable to infectious diseases, and epidemiological data show that its attributable mortality rate remains static or is rising, while declining for cardiovascular diseases and many cancers in developed countries [40]. Mortality in European adults varies from country to country and based on the age, it ranges from 4.5 to 5 per 100,000 in turkey and Georgia to 30 to 35 per 100,000 in Portugal and UK [41]. Near a half of under-five deaths worldwide are due to preventable diseases including pneumonia, diarrhea, and malaria with 2.2 million deaths in children under 5 years in 2012, in Nigeria, Democratic Republic of Congo, India, Pakistan, and China [42]. The overall prevalence of CAP in Africa is unknown, due to the lack of standardized protocols and reporting. A study in Uganda reported *Klebsiella pneumoniae* as the prevalent pathogen in neonates and *S. pneumoniae* was the most common etiological agent in those aged between

Outcome of pneumonia is still a health concern, mainly in developing countries, despite the development of new antibacterial agents. This phenomenon relays on the emerging antibiotic resistance of the pathogen on one hand and on host-related factors (impaired immunity, poor hygiene, age, malnutrition, comorbidities) on the other. Innovative approaches through better understanding of pathophysiology of the disease and environmental changes, early diagnosis techniques, multidisciplinary approach, and host-driven measures (behavior, accessibility to

Community-acquired pneumonias is the leading cause of death due to the infectious disease in both developed and developing world [22]. Developing countries are also the most affected due to many additional conditions such as poverty, low economic access to healthcare, lack of appropriate tools for early diagnosis, many socio-cultural barriers, and the unpreparedness against environmental changes. A study from Tanzania has identified the negative role of difficult diagnoses and comorbidities in the prognosis of CAP [46]. Children under 5 years and elderly are the most vulnerable population, and 30-day mortality has not been improved since the 1950s, despite the availability of new antibiotics [47]. CAP occurs in almost 1–10 per 1000 of the adult population each year and more commonly in extreme ages. According to the WHO European region report in 2010, lower respiratory tract infections ranked fifth in the global burden disease study [30]. The same report identified infectious diseases, childhood illnesses, and maternal causes of death as accounting for 70% of the burden of diseases in sub-Saharan Africa, while representing <20% in all others countries. Even reduced compared to two decades ago, the

health facilities) need to be developed to improve the control of respiratory mortality.

tion policies among other preventive measures to improve respiratory health [37–39].

**3. Community-acquired pneumonia (CAP): epidemiology, clinical** 

**feature, and treatment**

3 months and 5 years [43–45].

**3.1. CAP: epidemiology**

40 Contemporary Topics of Pneumonia

Pneumonia could result from infectious pathogens including bacteria, viruses, fungi, and parasites, or from noninfectious agents, of physical or chemical nature (aspiration pneumonia, gas inhalation). The main route for bacterial contamination is bronchogenic dissemination following microaspiration of pharyngeal secretions. Hematogenous spread follows bloodstream invasion by pathogens; and infection could also spread from contiguous tissues. In the alveolar space, host local defenses through humoral or cellular-mediated immune responses or mechanical processes (mucociliary escalator, cough reflex) when overwhelmed, allow the infection onset. The inflammation in the lung structures results in the release of mediators and accumulation of an exudate impairing the local immune system. The thickening of the alveolocapillary membrane alters the gas diffusion, inducing hypoxemia. The mismatch in the ventilation-perfusion ratio due to the reduced minute-ventilation increases the hypoxemia. Pneumococcal carriage in the posterior nasopharynx is a prerequisite for the development of pneumonia due to *S. pneumoniae*. Human to human transmission occurs through inhaled aerosols or close contact. The virulence of the pathogen is carried by factors allowing adhesion to the respiratory epithelium and released virulence factors such as pneumolysin and neuraminidase, which can damage the lung structures. The concentration of the pathogens is also a requirement for the onset of disease. Host immunity through humoral- and cell-mediated immunity is the main way of defense. Airway epithelium secretes also lactoferrin with the potential of deprecating the pathogen from iron, and then impairing the growth of the bacteria. Lysozyme and human defensins are along with cathelicidin-related antimicrobial peptides LL-37, also involved in the lysis of bacteria [49]. The classic evolution of acute pulmonary inflammatory response will turn in red hepatization, gray hepatization, and resolution. Main causes of CAP are *S. pneumoniae*, *M. pneumoniae*, *H. influenzae*, *C. pneumoniae*, *Legionella* sp., or respiratory virus with influenza A and B, respiratory syncytial (RSV), rhinovirus, and parainfluenza as the most encountered. Fungal infection mainly affects immunocompromised patients and parasitic infections are mainly endemic [50]. Clinical syndrome of condensation and radiological alveolar syndrome occur in few days. Pathogens implicated in nosocomial infection include a larger panel with methicillin-resistant staphylococcus aureus (MRSA), Enterobacteriaceae, and different types with a potential of resistance and difficult to treat infections.

Bronchoscopic aspirations are more relevant than sputum samples culture to minimize the

Pneumonia: A Challenging Health Concern with the Climate Change

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Chest radiograph demonstrating a peripheral airspace consolidation pattern is relevant in the diagnosis of pneumonia. Lung shadowing of lobar pattern associated to air bronchogram is common, while centrilobular and peribronchiolar opacity are defining the bronchopneumonia pattern. The lower lobes are most commonly affected. Recent literature illustrates the relevance of lung ultrasound in the diagnosis of CAP. A multicenter study in 14 European centers has shown a sensitivity of 93.4% and a specificity of 97.7% in the confirmation of the diagnosis [52].

The differential diagnosis should consider all illness expressed with dyspnea such as pulmonary embolism, COPD exacerbations, bronchiectasis, exacerbation of fibrosis, or with cough

CAP mortality remains high despite the development of new antibiotics and new tools for early-onset diagnosis. Main complications are sepsis and respiratory failure, but about 50% of CAP mortality in the first month is due to comorbidities [53]. Respiratory infections through hypoxemia and oxidative stress are a potential determinant of cardiovascular adverse events. The underlying atherosclerosis as shown by the increased rate of inflammatory biomarkers (fibrinogen, CRP, cytokines) in infectious status may impact on prothrombotic vascular conditions and subsequent cardiovascular ischemic diseases [54, 55]. The prognosis of acute myocardial infarction, cardiac arrhythmias, and heart failure is often worsened by respiratory

CAP is not simply a local but systemic inflammatory response as expressed by the measurable increase in serum biomarkers such as IL-6, IL-8, and TNF-alpha. To improve patients' outcomes, preventive measures are strongly recommended such as smoking cessation interventions and accurate screening of comorbidities. About a half of CAP mortality within the first month is due to the comorbidities such as cardiovascular complications, cancer, chronic lower respiratory diseases renal failure, and infections, mainly involving the elderly [58, 59]. Cardiovascular mortality contributes for almost 30% of deaths after CAP; that is the case of myocardial infarction in a multicenter study by Lichtman et al. reporting a 7.2% of CAP in patients admitted to the hospital with an acute myocardial infarction [60]. Cardiac arrhythmias are also observed sometimes induced by the use of macrolides alone or in combination therapy [61]. Respiratory infections were more frequent (19 vs. 6%) in a comparison study of

Empyema is a harmful complication of pneumonia occurring mostly in more vulnerable sub-

Preventive measures through behavioral changes such as smoking cessation and vaccination in vulnerable populations such as drepanocytosis patients, COPD, renal insufficiency patients with influenza, and pneumococcal vaccines need to be largely implemented to reduce the

stroke patients and control [62], suggesting the comorbidity of this condition.

likelihood of commensal flora.

and associated fever such as acute bronchitis.

**3.4. Complications of CAP and prevention**

infections according to few previous studies [55–57].

jects (comorbidities, immune disorders).

mortality rate.
