**2. Global epidemiology of acute LRTIs**

#### **2.1 Top causes of death**

The World Health Organization (WHO) estimated that 55.4 million people died worldwide in 2019, with the top 10 leading causes accounting for 55% of deaths [13]. Further,

*Physiological Role of Alveolar Macrophage in Acute Lower Respiratory Tract Infection… DOI: http://dx.doi.org/10.5772/intechopen.110509*

seven of these causes are non-communicable diseases (NCDs), with the first, second, and third leading causes being ischemic heart disease, stroke, and chronic obstructive pulmonary disease. The total number of deaths caused by all NCDs accounts for 74% of the total deaths in the world. However, among communicable diseases, acute LRTIs kill 2.6 million people worldwide, making them the fourth leading cause of death.

#### **2.2 Morbidity and mortality of acute LRTIs in children**

According to the analysis results of the Global Burden of Disease Study (GBD) in 2016, acute LRTIs caused 336 million episodes and 2.4 million deaths in 2016 [14]. The rates of episodes and deaths attributable to acute LRTIs in children under the age of 5 were 2.4 and 3.2 times higher, respectively, compared with those in people of all ages; in particular, the mortality rates in children were the highest in developing countries in sub-Saharan Africa and South Asia. However, worldwide deaths from acute LRTIs in children decreased by 36.4% between 2007 and 2017 [16]. The substantial improvement in mortality in children is suggested to be primarily due to the implementation of vaccines against *S. pneumoniae* and *Haemophilus influenzae*, antibiotic therapy, and continuous improvements in education, nutrition, water, sanitation, and hygiene [24].

### **2.3 Morbidity and mortality of acute LRTIs in the elderly**

Notably, the rates of episodes and deaths attributable to acute LRTIs in the elderly over the age of 70 were also 3.4 and 8.3 times higher, respectively, compared with those in people of all ages, but the mortality rates in older adults were globally higher than those in people of all ages [14]. Worldwide deaths from acute LRTIs in the elderly increased by 33.6% between 2007 and 2017 compared with those in children [16]. The deterioration of mortality in the elderly is likely associated with the extended longevity of the frail older population, chronic diseases, comorbidities, multiple medication use, and functional disability in high-income countries; further, it is associated with the adverse effects of air pollution, smoking, and alcohol consumption in low-income countries [24].

#### **2.4 Most common causative agent of pneumonia**

Acute LRTIs are responsible for inflammation of either the mucous membranes that line the bronchi or the lung tissue in one or both lungs, accompanied by infiltration and inflammation of the alveoli, leading to bronchitis or pneumonia, respectively [25]. Of the two conditions, pneumonia is the major cause of death, as it causes respiratory failure by filling the alveoli with fluid and pus resulting from inflammation [26]. Notably, pneumonia is caused by various pathogens, including bacteria, fungi, and viruses. *S. pneumoniae*, a Gram-positive bacterium, is the most common bacterial cause of pneumonia. In fact, across generations, *S. pneumoniae* accounted for approximately half of the pathogens that caused deaths in 2016, contributing to a higher number of deaths compared with all other major etiologies combined (respiratory syncytial virus, *H. influenzae* type b, and influenza) [14].

#### **2.5 Seasonal influenza**

Seasonal influenza epidemics occur every winter, annually resulting in 3–5 million cases of severe illness and 290,000–650,000 deaths from respiratory illness [15].

According to the analysis results of the GBD 2017, acute LRTIs attributable to influenza were estimated to have caused 55.5 million episodes, 9.5 million hospitalizations, and 145,000 deaths in 2017, and the highest mortality rates were observed, especially among adults over the age of 70 [17]. Of the influenza A and B viruses that cause seasonal epidemics, influenza A viruses, in particular, have a high mutagenic capacity to generate new strains that can escape from acquired immunity, which causes a pandemic every few decades. Further, the influenza A(N1H1)pdm09 strain emerged in April 2009 and caused a pandemic, globally resulting in 200,000 respiratory and 80,000 cardiovascular deaths that year [27].

### **2.6 COVID-19**

The ongoing pandemic is COVID-19, which is caused by SARS-CoV-2. Since the first case of COVID-19 was reported in Wuhan, China, in December 2019, the infection has rapidly spread worldwide and continues to be a global epidemic, regardless of the season. According to the WHO, as of January 2023, the confirmed cases of infected patients had reached approximately 750 million worldwide, and deaths had risen to >6.8 million [28]. As with other acute LRTIs, older adults are at a higher risk of severe illness or death from COVID-19, even after the Delta-virulent strain was replaced by the Omicron-attenuated strain [29–33].
