Pneumonia
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Pneumonia: Overview, Classification, Causes & Pathophysiology
Definition
Pneumonia is an acute infection of the lung parenchyma resulting in alveolar consolidation. The term encompasses a spectrum of entities that differ substantially in their epidemiology, microbiology, host risk factors, and prognosis.
Classification
The most clinically useful classification is based on the setting of acquisition, because this strongly predicts the likely pathogen and guides empiric therapy.
1. Community-Acquired Pneumonia (CAP)
Pneumonia developing in an individual who has not been hospitalized or resided in a long-term care facility in the preceding 14 days, or who develops symptoms within 48 hours of hospital admission.
2. Hospital-Acquired Pneumonia (HAP)
Pneumonia developing ≥48 hours after hospital admission that was not incubating at the time of admission. - Washington Manual of Medical Therapeutics
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Ventilator-Associated Pneumonia (VAP): HAP developing >48-72 hours after endotracheal intubation and mechanical ventilation. Approximately 3.5% of ventilated patients develop VAP vs. 0.5% of nonventilated inpatients. - Goldman-Cecil Medicine
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Non-Ventilator HAP (NV-HAP): Because most hospitalized patients are not ventilated, the majority of HAP is in fact NV-HAP. Risk factors include impaired consciousness, dysphagia, and enteral feeding. - Goldman-Cecil Medicine
3. Within CAP: Typical vs. Atypical
| Feature | Typical | Atypical |
|---|---|---|
| Onset | Abrupt (<1 week) | Insidious (days-weeks) |
| Cough | Productive, purulent | Dry, non-productive |
| Radiology | Lobar consolidation | Patchy, bilateral, interstitial |
| Gram stain | Organisms visible | Not visualized |
| Beta-lactam response | Usually sensitive | Intrinsically resistant |
| Common pathogens | S. pneumoniae, H. influenzae, S. aureus | Mycoplasma, Chlamydophila, Legionella, viruses |
- Quick Compendium of Clinical Pathology; Fishman's Pulmonary Diseases
Causative Organisms
CAP Pathogens
Bacterial (typical):
- Streptococcus pneumoniae - the single most common bacterial cause across all age groups
- Staphylococcus aureus (including CA-MRSA)
- Haemophilus influenzae
- Klebsiella pneumoniae (alcoholics, diabetics)
- Gram-negative bacilli (Pseudomonas aeruginosa in bronchiectasis/CF/severe COPD)
Atypical organisms (intracellular/cell-wall deficient):
- Mycoplasma pneumoniae - most common atypical pathogen; up to 15% of outpatient CAP
- Chlamydophila pneumoniae (C. pneumoniae)
- Legionella pneumophila - often outbreak-related, environmental water source exposure
- Chlamydophila psittaci (psittacosis - bird exposure)
- Coxiella burnetii (Q fever - cattle/cat exposure)
- Francisella tularensis (rabbit exposure)
Viral:
Viruses are identified in 23-25% of hospitalized CAP patients with modern PCR-based multiplex panels. Rhinovirus is the single most frequently detected pathogen overall in the CDC-EPIC study. Other key viruses:
- Influenza A/B
- Respiratory syncytial virus (RSV)
- Parainfluenza, metapneumovirus, adenovirus
- SARS-CoV-2
"The microbial etiology/pathogen is not identified in up to 60% of patients with CAP, even with PCR-based diagnostics." - Murray & Nadel's Respiratory Medicine
Fungal (mainly immunocompromised or endemic exposures):
- Pneumocystis jirovecii (PJP) - CD4 <200/mcL
- Histoplasma capsulatum (bat/bird droppings)
- Coccidioides (desert Southwest - sandstorm exposure)
- Blastomyces dermatitidis
- Aspergillus (prolonged corticosteroids, severe immunosuppression)
Host-Factor Pathogen Guide
| Host Condition | Key Pathogens |
|---|---|
| COPD | H. influenzae, M. catarrhalis, L. pneumophila |
| Alcoholism | S. pneumoniae, K. pneumoniae, anaerobes (aspiration), GNRs |
| Severe COPD/bronchiectasis/CF | Pseudomonas aeruginosa, Burkholderia cepacia, S. aureus |
| Neutropenia | Aerobic Gram-negative bacilli |
| Bird exposure | C. psittaci, Cryptococcus neoformans |
| Bat/bird droppings | Histoplasma capsulatum |
| Cattle/cat exposure | Coxiella burnetii |
| Rabbit exposure | Francisella tularensis |
| HIV CD4 <200 | P. jirovecii, M. tuberculosis, bacterial pneumonia |
- Quick Compendium of Clinical Pathology, Table 3.2; Murray & Nadel's
HAP/VAP Pathogens
HAP/VAP is caused by a shift in the oropharyngeal flora toward healthcare-adapted organisms. Common pathogens include Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, MRSA, Enterobacter species, and other MDR GNRs. Risk stratification for MDR pathogens (MRSA, MDR Pseudomonas, ESBL producers) is essential for empiric coverage decisions. - Fishman's Pulmonary Diseases
Pathophysiology
Route of Pathogen Entry
The vast majority of pneumonias arise from aspiration of oropharyngeal secretions into the lower respiratory tract (LRT). During sleep, ~50% of normal adults aspirate small volumes of oropharyngeal contents; this becomes more significant with dysphagia, reduced consciousness, or altered gag reflex. Organisms such as Mycoplasma, Chlamydophila, Legionella, and respiratory viruses instead enter via direct inhalation of droplet nuclei <5 μm that survive airborne suspension. - Murray & Nadel's Respiratory Medicine
Normal Host Defenses (and How They Fail)
Pneumonia is rare relative to the frequency of oropharyngeal colonization with potential pathogens, attesting to the effectiveness of pulmonary defenses:
- Anatomical barriers - Nasal turbulates, cough reflex, glottal closure
- Mucociliary escalator - Traps and clears particles; impaired by smoking, viral infection, air pollutants
- Antimicrobial peptides (defensins) - Synthesized by respiratory epithelial cells and phagocytes
- Surfactant proteins A and C - Inhibit bacterial binding and promote phagocytosis of S. pneumoniae and other bacteria
- Complement and immunoglobulin (especially IgA) - Prevent colonization; opsonic IgG antibodies are critical for phagocytosis of encapsulated organisms
- Alveolar macrophages - First responders; recognize pathogens via pattern recognition receptors (TLRs), triggering cytokine/chemokine production
When host defenses fail, bacteria colonizing the oropharynx (pathobionts) adhere to lower airway epithelium via specific adhesins (e.g., S. pneumoniae capsule + platelet-activating factor receptor; S. aureus adhesins to extracellular matrix proteins; GNR pili). Viral co-infection, smoking, and particulate pollutants upregulate these receptors and impair ciliary function, dramatically increasing infection risk. - Murray & Nadel's Respiratory Medicine
Inflammatory Response and Consolidation
Once bacteria establish in the alveolus, a cascade follows:
- Pattern recognition receptor activation (TLR, NLR) triggers cytokine/chemokine release
- Neutrophil recruitment produces the exudate that fills alveolar spaces (consolidation)
- Classic lobar pneumonia (especially pneumococcal) progresses through 4 histologic stages: congestion → red hepatization → grey hepatization → resolution
- In severe pneumonia, bilateral consolidation and disruption of alveolar-capillary integrity can progress to ARDS
Gas Exchange Abnormalities
Consolidation creates regions of shunt (perfused but not ventilated) and low V/Q areas. In mild-moderate pneumonia: shunt ~7.5%, low V/Q ~4.2%. In severe pneumonia requiring mechanical ventilation: shunt ~22%, low V/Q ~11%. The degree of shunt determines the response to supplemental O2 (high shunt fractions are relatively unresponsive). - Murray & Nadel's Respiratory Medicine (MIGET studies)
HAP Pathobiology
HAP arises from the same aspiration mechanism, but perturbations of the oral microbiome during illness allow pathogenic organisms to proliferate. Chemical analyses of tracheal aspirates identify gastrin and pepsin in up to two-thirds of intubated patients, confirming routine aspiration of gastric secretions. Some aspirations cause subclinical inflammation that resolves; others progress to frank infection. - Goldman-Cecil Medicine
Epidemiology (Key Numbers)
- CAP accounts for ~1.5 million annual ED visits and is a leading cause of hospital admission in the U.S.
- CAP is the 8th leading cause of death in the U.S. (4th worldwide for lower RTIs)
- Annual hospitalization rate: 649/100,000 adults; rises to 2093/100,000 for adults ≥65 years
- 23% of hospitalized CAP patients require ICU care
- ~1/3 of patients hospitalized for CAP die within 1 year; 1-year mortality approaches 50% for ICU admissions
- HAP is the most common and morbid healthcare-associated infection; affects ~1 in 100 hospitalized patients
- Fishman's Pulmonary Diseases and Disorders
Special Populations
| Population | Key Points |
|---|---|
| Children <2 yr | S. pneumoniae and RSV dominate |
| Older children/young adults | S. pneumoniae, viruses, M. pneumoniae |
| Elderly | Higher incidence of aspiration pneumonia, H. influenzae, group B streptococci, GNRs; lower relative M. pneumoniae proportion |
| Alcoholics | Increased aspiration risk; S. pneumoniae, K. pneumoniae, anaerobes |
| Smokers | Double the CAP risk; responsible for ~1/3 of cases |
| COPD | H. influenzae, S. pneumoniae; ICS use increases pneumonia risk |
| CF | Infancy: S. aureus, nontypeable H. influenzae; by age 18: 80% colonized with P. aeruginosa |
| HIV (any CD4) | Bacterial pneumonia most common; >2 episodes/year = AIDS-defining condition |
- Murray & Nadel's Respiratory Medicine
Sources: Murray & Nadel's Textbook of Respiratory Medicine | Fishman's Pulmonary Diseases and Disorders | Goldman-Cecil Medicine | Quick Compendium of Clinical Pathology | Washington Manual of Medical Therapeutics
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