Due to the difference in the metabolism and susceptibility of hosts, respiratory diseases can be caused by one or many agents (occupational and environmental agents diet, air-pollutants, toxic aerosols, microbes ¹) ². Identifying these causes can be difficult due the manifestation period of the symptoms ². It was reported that genetics also play a critical role in the origin and development of respiratory diseases³. Due to these reasons, chronic respiratory diseases can be the result of the combination of several factors ^{2 3}.

The most common and critical respiratory diseases are: Infectious diseases (pneumonia, bronchitis and influenza), cystic fibrosis, asthma, chronic obstructive pulmonary diseases (COPD) and lung cancer ¹.

1. Infectious diseases

 Microbial infections play an important role in the progression of chronic lung diseases. They can lead to a progressive destruction of lung tissue until a respiratory failure ⁴. Lower respiratory infections can be deadly despite some drug therapies. Infectious diseases such as pneumonia remain a major cause of mortality ⁴. The important factor for eliminating bacteria from lungs is to locally concentrate the antimicrobial agents in the lung. Thus the alveolar and bronchial epithelium is the targeted site for drug delivery and therapy ⁴ . Infectious diseases are particularly devastating in infants and elderly populations ⁵. The most common respiratory infectious diseases are pneumonia, bronchitis and influenza ¹.

1.1. Pneumonia

Pneumonia is considered as one of the most problematic bacterial diseases encountered in clinical environments ⁵. In the United States, over 1 million individuals require hospitalization due to severe pneumonia infections every year ⁵. This infectious disease is an inflammatory disorder of the lung parenchyma ⁵. It can be divided in community, nursing-home and hospital acquired pneumonia ⁵. Many micro-organisms can cause pneumonia, e.g. viruses, bacteria, fungi, parasites ⁵. The capability of a microorganism to cause this disease depends on the inoculum size and virulence as well as the host immune system ⁵. Pneumonia is usually treated with anti-microbial agents ⁵.

1.2. Bronchitis

Acute bronchitis is an infection of the tracheobronchial tree inducing a productive cough ⁶. The diagnosis of acute bronchitis is mainly clinical ⁶. Bronchitis is mainly caused by viruses (85-95%), but can also be caused by bacteria ⁶. The most common viruses are rhinovirus, adenovirus, influenza virus types A and B, and parainfluenza virus ⁶. The most commonly involved bacteria in bronchitis are Mycoplasma pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Bordetella pertussis ⁶. Antibiotics confer only minimal benefits on patients with bronchitis ⁶. Chronic bronchitis on the contrary is mostly caused by smoke ⁷. It is characterized by irreversible airflow obstruction and persistent inflammation due to noxious environmental stimuli, usually cigarette smoke. Chronic bronchitis is the third leading cause of death and disease burden worldwide ⁷.

1.3. Influenza

Human influenza virus infection causes transient tracheo-bronchitis ⁸. It corresponds to the attachment of the virus to tracheal and bronchial epithelial cells ⁸. This infection can extend to the alveoli with secondary bacterial infection, which can result in severe pneumonia ⁸. Human influenza A virus includes subtypes H1N1, H2N2, and H3N2 ⁸. Transmission of human influenza virus occurs by inhalation of infectious droplets or airborne droplet nuclei, and by indirect contact followed by self-inoculation of the upper respiratory tract or conjunctival mucosa ⁸.

1.4. Tuberculosis ^9,10

Tuberculosis is an infection disease caused by the bacterium Mycobacterium tuberculosis. The agent is spread in the air (e.g. by coughing). Tuberculosis is one of the top ten causes of death worldwide. Pharmacological treatments consist of antibiotics. There are effective treatments that were reported to have a global treatment success rate of about 85% for new cases of tuberculosis. However, drug-resistant tuberculosis is a public health threat. Without effective treatments, the mortality rates are very high. The UN aims to end the tuberculosis epidemic by 2030.

2. Cystic fibrosis

Cystic fibrosis is a genetic, autosomal recessive disorder ⁴. It is caused by a dysfunction of the epithelial chloride channel ⁴. The major cause of mortality results from airway disease ⁴. It leads to mucus overproduction and distortion of the mucociliary clearance ⁴. As a result, the mucus plugs the airway which causes chronic inflammatory changes and bacterial colonization ⁴. Chronic medications and airway clearance therapies are recommended as treatments ¹¹, but their efficacity has still to be proven.  

3. Asthma

Asthma is one of the most common obstructive lung diseases which is nonetheless reversable with patients who are able to improve their breathing flow rates. (ref Dorian 2.). More than 250 substances are reported to cause occupational asthma ². Asthma is a lung disease that occurs by reversible airway obstruction, airway inflammation and an increased response of the airway to many stimuli. 10 Million  people are estimated to have asthma in the United States ¹². All patients with asthma are at risk of developing exacerbations ¹³.Asthma is considered a highly complex disease that is still poorly understood ¹⁴. The severity of asthma exacerbations determines the treatment. Treatments consist mainly of inhaled bronchodilators that reduce airway inflammation and prevent future relapses with early administration of systemic corticosteroids ¹³. 

4. Chronic Obstructive Pulmonary Disease

 Chronic obstructive pulmonary disease (COPD) includes several progressive lung diseases, i.e. emphysema, chronic bronchitis, and refractory asthma. A typical and common symptom is increased breathlessness. Other common symptoms are chronic cough and sputum (mucous) production. Exposure to tobacco smoke (active smoking or secondhand smoke) is considered as the main cause of chronic obstructive pulmonary disease ¹⁵. Nevertheless, occupational dusts (e.g. cotton, coal, beryllium, silica or other mineral dusts) can contribute to chronic airflow limitation ².  

 

5. Lung Cancer

Lung cancer can be divided into two major types, i.e. small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC) ¹⁶¹⁷. The predominant risk factor is tobacco use that causes up to 90% of all lung cancers ¹⁷. Other risk factors are secondhand smoke exposure, environmental exposures, and comorbidities ¹⁶¹⁷. Environmental exposure includes domestic exposure to biomass fuels, occupational exposure (e.g. asbestos), air pollution, arsenic in drinking water and residential radion ¹⁶¹⁷. COPD is the most common morbidity with a prevalence between 30 and 70%. Genetics, i.e. familial and genetic variations, can predispose to lung cancer, even for nonsmokers ¹⁶¹⁷. The most common identified genetic mutations are mutations in the epidermal growth factor receptor (EGRF) and KRAS genes ¹⁶¹⁷. A minimum of 12 substances are found to be human lung carcinogens ². Occupational exposure is estimated to cause 5% of lung cancers in the United States ². The majority of these cancers are caused by asbestos, followed by radon, silica, chromium, cadmium, nickel, arsenic, and beryllium. Cigarette smoke and asbestos interact in causing bronchogenic carcinomas ². 

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