Severe Pulmonary Cryptococcosis in an Immunocompetent Patient Presenting With Acute Respiratory Failure

Pulmonary cryptococcosis may present with nonspecific respiratory symptoms and, in patients with underlying reactive airway disease, can act as a trigger for refractory asthma exacerbation leading to acute respiratory failure, even in immunocompetent individuals. A 60-year-old immunocompetent male, with a negative HIV test, no chronic immunosuppressive therapy, and a remote brief corticosteroid course well below the threshold for clinically significant immunosuppression, presented with approximately two months of progressive dyspnea and cough after multiple treatment courses for presumed asthma exacerbations and bronchitis without improvement. His condition deteriorated during hospitalization, requiring noninvasive ventilation followed by endotracheal intubation for acute hypoxic respiratory failure driven by a refractory asthma exacerbation. The clinical presentation closely mimicked bacterial pneumonia superimposed on asthma exacerbation, with CT imaging demonstrating bronchial wall thickening and mucous plugging, which initially precluded suspicion of a fungal etiology. Serum cryptococcal antigen was negative. An extensive noninvasive infectious workup remained unrevealing, and broad-spectrum antibiotics and bronchodilator therapy failed to produce improvement. On hospital day five, bronchoscopy with bronchoalveolar lavage (BAL) was performed, given persistent hypoxemia and diagnostic uncertainty, with BAL fungal culture growing Cryptococcus neoformans and establishing pulmonary cryptococcosis as the underlying trigger of the refractory asthma exacerbation. CNS dissemination was excluded clinically on the basis of intact mentation and absent neurological symptoms throughout the hospital course. Infectious disease consultation determined that respiratory failure was attributable to cryptococcal-triggered asthma exacerbation rather than disseminated disease, and fluconazole monotherapy was initiated accordingly. The patient was successfully extubated on hospital day six and demonstrated steady clinical improvement over the following week with high-flow oxygen support via vapotherm before being discharged on long-term fluconazole. This case highlights the importance of considering fungal etiologies as triggers of refractory asthma exacerbation and emphasizes early bronchoscopy with BAL when noninvasive evaluation is unrevealing in patients with persistent unexplained airway disease.