Aspiration pneumonia pathophysiology

Aspiration pneumonia is a common pneumonia among patients with risk factors including neurologic diseases. Microaspiration and macroaspiration of different materials are the primary cause of aspiration pneumonia. The mechanism behind damage of lung due to aspiration depends on the content of aspirate and the response of lung tissue to the content. Host factors including mucociliary clearance, cough reflex, and immune system might be impaired. Chemical pneumonitis usually occurs following aspiration of materials that are toxic to pulmonary tissue. There might be no bacterial or viral organisms involved. It is mostly associated with aspiration of gastric acid. In case of oropharyngeal secretions the damage is due to bacteria infecting and inducing inflammation in lung tissues. Foreign body aspiration might present acutely with mechanical obstruction or chemical pneumonitis. Lipoid pneumonia is caused by aspiration of mineral oil when used for constipation treatment. Following oil aspiration there is an inflammatory response with regional edema, acute cough, fever, and dyspnea. Patients with genetic syndromes and paralysis of lower cranial nerves might be prone to aspiration pneumonia. On gross pathology, different aspirated particles might be seen. On microscopic histopathological analysis, aspirated material fragments, inflammation, fibrosis, and skeletal muscle fibers might be seen.

To understand the pathogenesis we have to review following physiological facts regarding aspiration pneumonia:^{[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]}

Inhalation of aerosolized droplets of 0.5 to 1 micrometer is the most common pathway of acquiring pneumonia. A few bacterial and viral infections are transmitted in this fashion. The lung can normally filter out particles between 0.5 to 2 micrometer by recruiting the alveolar macrophages.

Aspiration of oropharyngeal contents containing pathogenic microorganisms is one of the mechanisms of acquiring pneumonia. It most commonly occurs in normal persons during sleep, in unconscious persons due to gastroesophageal reflux or impaired gag reflex and cough reflex.

Several strategies are evolved to evade host defense mechanisms and facilitate spreading before establishing an infection.

• Influenza virus possesses neuraminidases for cleavage of sialic acid residues on the cell surface and viral proteins, which prevent aggregation and facilitate propagation of viral particles.

• Chlamydophila pneumoniae induces complete abortion of cilia motions which assists colonization at the respiratory epithelium.

• Mycoplasma pneumoniae produces a virulence factor with ADP-ribosylating activity which is responsible for airway cellular damage and mucociliary dysfunction.

• Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis produce proteases that split mucosal IgA.

• Streptococcus pneumoniae possesses pneumolysin that aid the bacteria during colonization, by facilitating adherence to the host, during an invasion by damaging host cells, and during infection by interfering with the host immune response.

• The lungs can normally filter out large droplets of aerosols.
• Smaller droplets of the size of 0.5 to 2 micrometer are deposited on the alveoli and then engulfed by alveolar macrophages.
• These macrophages release cytokines and chemokines, which also includes tumor necrosis factor-alpha, interleukin-8 and LTB4.
• The neutrophils are recruited by these cells to eliminate these microorganisms.

• The cilia lining the respiratory epithelium serve to move secreted mucus containing trapped foreign particles including pathogens towards the oropharynx for either expectoration or swallowing.
• Elevated incidence of pneumonia in patients with genetic defects affecting mucociliary clearance such as primary ciliary dyskinesia suggests its role in the pathogenesis of community-acquired pneumonia.

• Cough, together with mucociliary clearance, prevent pathogens from entering the lower respiratory tract.
• Cough suppression or cough reflex inhibition seen in patients with cerebrovascular accidents and drug overdosages is associated with an enhanced risk for aspiration pneumonia.
• Another relation to cough is genetic polymorphisms in the angiotensin-converting enzyme (ACE) gene.
• The role of cough in preventing pneumonia may be explained by a higher risk for developing pneumonia in homozygotes carrying deletion/deletion (DD) genotype who are found to have lower levels of bradykinin and tachykinins such as substance P.

• Pathogen-associated molecular patterns (PAMPs) are initially recognized by Toll-like receptors (TLRs) and other pattern-recognition receptors (PRRs) of the innate immune system.
• Effectors in the acquired immune system are involved in elimination of microorganisms and generation of immunological memory.
• Other components in the immune system such as complement system, cytokines, and collectins, also mediate the defense against microorganisms causing pneumonia.

• Chemical pneumonitis usually occurs following aspiration of materials that are toxic to pulmonary tissue. There might be no bacterial or viral organisms involved. It is mostly associated with aspiration of gastric acid. 
• Following aspiration, there is onset of respiratory distress and cyanosis within 2 hours.
• In animal and autopsy studies, following gastric acid aspiration, atelectasis, peribronchial hemorrhage, pulmonary edema, and degeneration of bronchial epithelial cells initiates within three minutes. Release of proinflammatory cytokines, especially tumor necrosis factor-alpha (TNF) and interleukin-8 causes polymorphonuclear leukocytes and fibrin to fill the alveolar spaces after four hours. The lung become edematous and hemorrhagic with alveolar consolidation.

• Another form of aspiration pneumonia is caused by less virulent oral bacteria that normally colonized in the upper airways or stomach.
• Anaerobic bacteria are more involved in aspiration pneumonia.
• Peptostreptococcus, Fusobacterium nucleatum, Prevotella, Bacteroides melaninogenicus, and other Bacteroides spp are the major pathogens that cause pulmonary infections following aspiration. However, the majority have mixed aerobe and anaerobe infections.

• Foreign body aspiration might present acutely with mechanical obstruction or chemical pneumonitis.
• Foreign body aspiration is more common in children from one to three years of age.

• Lipoid pneumonia is caused by aspiration of mineral oil when used for constipation treatment.
• Patients usually have risk factors for aspiration.
• Following oil aspiration there is an inflammatory response with regional edema and acute cough, fever, and dyspnea.
• Fibrous tissue encapsulates aspirated oils and develop intraalveolar hemorrhage. They will presents with a mass seen on imaging in an asymptomatic patient.

• There are no genetic causes of aspiration pneumonia.
• However, patients with genetic syndromes and paralysis of following lower cranial nerves might be prone to aspiration pneumonia.^[16][17]
  • Cranial nerve 9 (glossopharyngeal)
  • Cranial nerve 10 (vagal)
  • Cranial nerve 11 (accessory)
  • Cranial nerve 12 (hypoglossal)
• Associated genetic syndromes are as follow:
  • Cerebral palsy
  • Amyotrophic lateral sclerosis (ALS)
  • Spinal muscular atrophy
  • Bulbospinal muscular atrophy (BSMA)
  • Unclassified motor neuron diseases such as:
    • Sandhoff disease
    • Triple-A syndrome
    • Brown-Vialetto-Van Lare-syndrome
  • Hereditary neuropathy

• On gross pathology, different aspirated particles might be seen.

• On microscopic histopathological analysis, aspirated material fragments, inflammation, fibrosis, and skeletal muscle fibers might be seen.

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