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Background: Severe coccidioidomycosis presenting with respiratory failure is an uncommon manifestation of disease. Current knowledge of this condition is limited to case reports and small case series. Methods: A retrospective multicenter review of patients with coccidioidomycosis-associated acute respiratory distress syndrome (CA-ARDS) was conducted. It assessed clinical and laboratory variables at the time of presentation, reviewed the treatment course, and compared this cohort with a national database of patients with noncoccidioidomycosis ARDS. Survivors and nonsurvivors of coccidioidomycosis were also compared to determine prognostic factors. Results: In this study, CA-ARDS (n = 54) was most common in males, those of Hispanic ethnicity, and those with concurrent diabetes mellitus. As compared with the PETAL network database (Prevention and Early Treatment of Acute Lung Injury; n = 1006), patients with coccidioidomycosis were younger, had fewer comorbid conditions, and were less acidemic. The 90-day mortality was 15.4% for patients with coccidioidomycosis, as opposed to 42.6% (P < .0001) for patients with noncoccidioidomycosis ARDS. Patients with coccidioidomycosis who died, as compared with those who survived, were older, had higher APACHE II scores (Acute Physiology and Chronic Health Evaluation), and did not receive corticosteroid therapy. Conclusions: CA-ARDS is an uncommon but morbid manifestation of infection. When compared with a national database, the overall mortality appears favorable vs other causes of ARDS. Patients with CA-ARDS had a low overall mortality but required prolonged antifungal therapy. The utility of corticosteroids in this condition remains unconfirmed.
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Introduction: Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is a disease phenotype that shares T helper lymphocyte cell Th1/neutrophilic/non-Type-2 Inflammation pathways thought to be key in COPD and Th2/eosinophilic/Type-2 inflammatory pathways of asthma. The pharmacology of treating ACOS is challenging in severe circumstances.Areas covered: This review evaluates the stepwise treatment of ACOS using pharmacological treatments used in both COPD and asthma. The most common medications involve the same inhalers used to treat COPD and asthma patients. Advanced stepwise therapies for ACOS patients are based on patient characteristics and biomarkers. Very few clinical trials exist that focus specifically on ACOS patients.Expert opinion: After inhalers, advanced therapies including phosphodiesterase inhibitors, macrolides, N-acetylcysteine and statin therapy for those ACOS patients with a COPD appearance and exacerbations are available. In atopic ACOS patients with exacerbations, advanced asthma therapies (leukotriene receptor antagonists and synthesis blocking agents.) are used. ACOS patients with elevated blood eosinophil/IgE levels are considered for immunotherapy or therapeutic monoclonal antibodies blocking specific Th2/Type-2 interleukins or IgE. Symptom control, stabilization/improvement in pulmonary function and reduced exacerbations are the metrics of success. More pharmacological trials of ACOS patients are needed to better understand which patients benefit from specific treatments.Abbreviations: 5-LOi: 5-lipoxygenase inhibitor; ACOS: asthma - COPD overlap syndrome; B2AR: Beta2 adrenergic receptors; cAMP: cyclic adenosine monophosphate; cGMP: cyclic guanosine monophosphate; CI: confidence interval; COPD: chronic obstructive pulmonary disease; CRS : chronic rhinosinusitis; cys-LT: cysteinyl leukotrienes; DPI: dry powder inhaler; EMA: European Medicines Agency; FDA: US Food and Drug Administration; FDC: fixed-dose combination; FeNO: exhaled nitric oxide; FEV1: forced expiratory volume in one second; FVC: forced vital capacity; GM-CSF: granulocyte-macrophage colony-stimulating factor; ICS : inhaled corticosteroids; IL: interleukin; ILC2: Type 2 innate lymphoid cells; IP3: Inositol triphosphate; IRR: incidence rate ratio; KOLD: Korean Obstructive Lung Disease; LABA: long-acting B2 adrenergic receptor agonist; LAMA: long-acting muscarinic receptor antagonist; LRA: leukotriene receptor antagonist; LT: leukotrienes; MDI: metered-dose inhalers; MN: M-subtype muscarinic receptors; MRA: muscarinic receptor antagonist; NAC: N-acetylcysteine; NEB: nebulization; OR: odds ratio; PDE: phosphodiesterase; PEFR: peak expiratory flow rate; PGD2: prostaglandin D2; PRN: as needed; RR: risk ratio; SABA: short-acting B2 adrenergic receptor agonist; SAMA: short-acting muscarinic receptor antagonist; SDMI: spring-driven mist inhaler; Th1: T helper cell 1 lymphocyte; Th2: T helper cell 2 lymphocytes; TNF-α: tumor necrosis factor alpha; US : United States.
