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Introduction: Non-specific pattern (NSP) is a subgroup of preserved ratio impaired spirometry (PRISm) that requires a normal total lung capacity measurement. NSP has been historically classified as being an obstructive lung disease pattern. There has been heightened interest and investigation into PRISm recently as it has been associated with an increased likelihood of developing chronic obstructive pulmonary disease (COPD). Given the inherent challenges of understanding the clinical significance of the NSP, the aim of this study was to further explore the clinical characteristics of patients with this pulmonary function test pattern. Material and methods: We identified 111 and 79 subjects using pre-bronchodilator (pre-BD) and post-bronchodilator (post-BD) values, respectively, that met criteria for NSP. The outpatient medical records were retrospectively reviewed for associated diagnoses that were then clustered into ‘obstructive’ or ‘non-obstructive’ groups based on the treating physician's primary pulmonary clinical diagnosis. Results: Within this NSP cohort, cough, wheezing and sputum production were documented more frequently in those with an obstructive lung disease diagnosis. Whether identified using pre-BD or post-BD spirometric values, those with NSP and a positive BD response were more likely to carry an obstructive lung disease diagnosis. Conclusion: Approximately one third of patients with NSP in this study were not given an obstructive lung disease diagnosis by their clinician, which supports the classification of NSP as not an exclusively obstructive lung disease pattern. However, the presence of supporting clinical symptoms, such as cough with sputum production and wheeze, and/or a positive BD response on PFT, support a diagnosis of obstruction in patients with NSP. Resumen: Introducción: El patrón inespecífico constituye un subgrupo de alteraciones de la espirometría con conservación de la relación (PRISm, siglas en inglés) que precisa de una medición de la capacidad pulmonar total normal; históricamente se ha clasificado como un patrón de neumopatía obstructiva. En épocas recientes se ha intensificado el interés en las PRISm y su investigación, ya que se ha asociado a un aumento de la probabilidad de aparición de una enfermedad pulmonar obstructiva crónica (EPOC). Dadas las dificultades inherentes que conlleva interpretar la importancia clínica del patrón inespecífico, el objetivo de este estudio consistió en explorar con más detalle las características clínicas de los pacientes con dicho patrón en las pruebas de la función pulmonar. Material y métodos: Se identificaron 111 y 79 sujetos empleando valores prebroncodilatador y posbroncodilatador, respectivamente, que cumplieron los criterios de patrón inespecífico. Se revisaron retrospectivamente las historias clínicas ambulatorias para detectar diagnósticos asociados que después se agregaron en grupos «obstructivos» o «no obstructivos» en función del diagnóstico clínico pulmonar primario del médico. Resultados: En esta cohorte de pacientes con patrones inespecíficos, se documentó una mayor incidencia de tos, sibilancias y producción de esputo entre los que tenían un diagnóstico de neumopatía obstructiva. Los pacientes con patrón inespecífico y una respuesta positiva al broncodilatador, que hubiesen sido identificados con valores pre o posbroncodilatador, tenían más probabilidades de haber recibido un diagnóstico de neumopatía obstructiva. Conclusión: Aproximadamente un tercio de los pacientes con patrón inespecífico de este estudio no habían recibido un diagnóstico de neumopatía obstructiva, dato que avala no clasificar los patrones inespecíficos exclusivamente en las neumopatías obstructivas. Sin embargo, la presencia de síntomas clínicos indicativos, como tos productiva y sibilancias, o una respuesta positiva al broncodilatador en las pruebas de la función pulmonar, sustenta un diagnóstico de obstrucción en los pacientes con patrón inespecífico.

Abstract Background Few therapies exist to treat severe COVID‐19 respiratory failure once it develops. Given known diffuse pulmonary microthrombi on autopsy studies of COVID‐19 patients, we hypothesized that tissue plasminogen activator (tPA) may improve pulmonary function in COVID‐19 respiratory failure. Methods A multicenter, retrospective, observational study of patients with confirmed COVID‐19 and severe respiratory failure who received systemic tPA (alteplase) was performed. Seventy‐nine adults from seven medical centers were included in the final analysis after institutional review boards' approval; 23 were excluded from analysis because tPA was administered for pulmonary macroembolism or deep venous thrombosis. The primary outcome was improvement in the PaO2/FiO2 ratio from baseline to 48 h after tPA. Linear mixed modeling was used for analysis. Results tPA was associated with significant PaO2/FiO2 improvement at 48 h (estimated paired difference = 23.1 ± 6.7), which was sustained at 72 h (interaction term p