Does Interstitial Lung Disease (ILD) increase the risk of infections?

Does Interstitial Lung Disease Increase Risk of Infections?

Yes, patients with ILD have a substantially increased risk of infections, driven by both the underlying disease pathophysiology and the immunosuppressive treatments required to manage it.

Infection Risk from the Disease Itself

ILD fundamentally compromises pulmonary defense mechanisms, creating an environment conducive to infection:

• Structural lung damage from fibrosis and inflammation disrupts normal mucociliary clearance and alveolar macrophage function, allowing pathogens to establish infection more easily 1, 2
• Mortality impact is substantial: patients with RA-ILD demonstrate 10-year mortality of 60.1% versus 34.5% in RA patients without ILD, with infections being a major contributor to this excess mortality 3
• Concurrent infection is recognized as a serious complication and one of the major factors that exacerbates ILD progression 4

Infection Risk from Immunosuppressive Treatment

The medications used to treat ILD significantly amplify infection susceptibility:

• Immunosuppressant use is directly associated with increased infection rates and higher numbers of isolated pathogens in ILD patients 4
• Gram-negative bacteria predominate in ILD patients receiving anti-infection treatment, whether hospital-acquired or community-acquired, with the five most common pathogens being Klebsiella pneumoniae (31.7%), Pseudomonas aeruginosa (20.6%), Acinetobacter (12.7%), Enterobacter cloacae (8.2%), and Staphylococcus aureus (7.8%) 4
• Immunosuppressive medications have the potential to result in substantial, and perhaps life-threatening, bacterial infections, though specific risk quantification for ILD populations remains limited 5

Specific High-Risk Populations

Certain ILD subtypes carry particularly elevated infection risk:

• Patients with connective tissue disease-associated ILD (CTD-ILD) face dual risk from both autoimmune disease activity and immunosuppressive therapy 3
• Systemic sclerosis patients with ILD show standard mortality rates increasing from 2.2 times (no fibrosis) to 8.0 times (>25% fibrosis), with infections contributing significantly 3
• Patients on combination immunosuppression (anti-TNF plus immunomodulator) demonstrate even greater vulnerability 3

Viral and Fungal Considerations

Beyond bacterial infections, other pathogens pose significant threats:

• Viral pathogens show the highest association with ILD pathogenesis and acute exacerbations, though fungal and bacterial organisms are also implicated 1
• Fungal infections accounted for 65 of 371 pathogen strains (17.5%) isolated from hospitalized ILD patients 4
• Infections have been theorized to play a role both in ILD pathogenesis and as potential triggers of acute exacerbations 1

Critical Clinical Pitfalls

Avoid underestimating infection risk in seemingly stable ILD patients, as immunosuppression creates persistent vulnerability even during quiescent disease phases 6. The American College of Rheumatology emphasizes that maintenance immunosuppressive therapy must continue in quiescent CTD to prevent relapse, but this necessitates ongoing infection vigilance 6.

Do not delay empiric antibiotic coverage when infection is suspected, as mortality in acute exacerbation of ILD (AE-ILD) is high without prompt intervention 7. Emergency management includes intravenous antibiotics alongside systemic steroids 7.

Recognize that drug-induced ILD can mimic infectious exacerbation, and the American College of Rheumatology suggests considering drug-induced ILD in any CTD-ILD patient who progresses despite appropriate therapy 8.

Practical Antibiotic Selection

Based on pathogen distribution and resistance patterns:

• Aminoglycosides and carbapenems demonstrate lower antibiotic resistance rates and should be prioritized for secondary infections in ILD patients 4
• Anti-MRSA/MRCNS coverage should be considered when Staphylococcus infection is suspected, given S. aureus accounts for 7.8% of bacterial isolates 4
• Antipseudomonal coverage is essential given P. aeruginosa represents 20.6% of bacterial pathogens in this population 4