Abstract Background Acute Respiratory Distress Syndrome (ARDS) is a severe inflammatory lung injury usually resulting from identifiable direct (e.g., pneumonia, aspiration) or indirect (e.g., sepsis, trauma) insults. Diagnostic criteria include an acute onset of respiratory failure within one week of a known trigger, bilateral infiltrates on imaging, and hypoxemia not fully explained by cardiac dysfunction. However, up to 15% of ARDS cases occur without a defined precipitant, categorized as idiopathic ARDS or acute interstitial pneumonia. Cigarette smoking has been implicated as a modifiable risk factor that increases susceptibility by priming alveolar and endothelial tissue for exaggerated inflammatory responses. Here, we present a rare case of severe, ultimately fatal ARDS in a chronic smoker without an identifiable cause, suggesting that smoking may act as a silent predisposing factor. Case Presentation A 78-year-old woman with atrial fibrillation, hypertension, hypothyroidism, and a 35-pack-year smoking history presented with prosthetic joint infection of the left knee due to Pseudomonas aeruginosa. She underwent revision total knee arthroplasty and was initially stable postoperatively. Despite broad-spectrum antibiotic therapy, inflammatory markers continued to rise (CRP 168→421 mg/L; WBC 23-25 ×10³/μL). Serial chest imaging revealed progressive bilateral ground-glass opacities consistent with ARDS. Echocardiography demonstrated preserved ejection fraction (55-60%) and no valvular or pulmonary vascular abnormalities, ruling out cardiogenic pulmonary edema. Extensive infectious workup, including blood, wound, bronchoalveolar cultures, and viral panels, remained negative. The patient developed worsening hypoxemia requiring high-flow oxygen and subsequent intubation. Despite corticosteroids, antibiotics, and maximal supportive therapy, her respiratory failure and renal dysfunction progressed, necessitating continuous venovenous hemodialysis. With no identifiable infectious or embolic source, the clinical picture was consistent with idiopathic ARDS. After family discussions, she was compassionately extubated and died. Discussion This case exemplifies idiopathic or “no-cause” ARDS, a rare but recognized clinical entity. Chronic smoking may have contributed to a “primed” inflammatory state, in which oxidative stress, endothelial dysfunction, and cytokine activation predisposed the patient to disproportionate lung injury from minor physiological stressors such as her surgery. This mechanism aligns with emerging evidence linking smoking exposure to subclinical alveolar injury and increased ARDS susceptibility, even in the absence of a major precipitating insult. Conclusion ARDS can develop in the absence of a clear precipitating event. Chronic cigarette smoking may serve as an underrecognized risk modifier, enhancing vulnerability to exaggerated inflammatory lung injury. Awareness of this association may aid in early recognition, risk stratification, and the development of preventive strategies among high-risk individuals-particularly in the perioperative setting. This abstract is funded by: None
Hossain et al. (Fri,) studied this question.