BackgroundPatients with chronic lung disease (CLD), such as asthma or chronic obstructive pulmonary disease, were expected to have an increased risk of clinical manifestations and severity of ...COVID-19. However, these comorbidities have been reported less frequently than expected. Chronic treatment with inhaled corticosteroids (ICS) may impact the clinical course of COVID-19. The main objective of this study is to know the influence of chronic treatment with ICS on the prognosis of COVID-19 hospitalized patients with CLD.MethodsA multicenter retrospective cohort study was designed, including patients hospitalized with COVID-19. Epidemiological and clinical data were collected at admission and at seven days, and clinical outcomes were collected. Patients with CLD with and without chronic treatment with ICS were compared.ResultsTwo thousand five hundred ninety-eight patients were included, of which 1,171 patients had a diagnosis of asthma and 1,427 of COPD (53.37% and 41.41% with ICS, respectively). No differences were found in mortality, transfer to ICU, or development of moderate-severe ARDS. Patients with chronic ICS had a longer hospital stay in both asthma and COPD patients (9 vs. 8 days, p = 0.031 in asthma patients), (11 vs. 9 days, p = 0.018 in COPD patients); although they also had more comorbidity burden.ConclusionsPatients with chronic inhaled corticosteroids had longer hospital stays and more chronic comorbidities, measured by the Charlson comorbidity index, but they did not have more severe disease at admission, evaluated with qSOFA and PSI scores. Chronic treatment with inhaled corticosteroids had no influence on the prognosis of patients with chronic lung disease and COVID-19.
We aimed to determine the impact of steroid use in COVID-19 in-hospital mortality, in a retrospective cohort study of the SEMICOVID19 database of admitted patients with SARS-CoV-2 ...laboratory-confirmed pneumonia from 131 Spanish hospitals. Patients treated with corticosteroids were compared to patients not treated with corticosteroids; and adjusted using a propensity-score for steroid treatment. From March–July 2020, 5.262 (35.26%) were treated with corticosteroids and 9.659 (64.73%) were not. In-hospital mortality overall was 20.50%; it was higher in patients treated with corticosteroids than in controls (28.5% versus 16.2%, OR 2.068 95% confidence interval; 1.908 to 2.242; p = 0.0001); however, when adjusting by occurrence of ARDS, mortality was significantly lower in the steroid group (43.4% versus 57.6%; OR 0.564 95% confidence interval; 0.503 to 0.633; p = 0.0001). Moreover, the greater the respiratory failure, the greater the impact on mortality of the steroid treatment. When adjusting these results including the propensity score as a covariate, in-hospital mortality remained significantly lower in the steroid group (OR 0.774 0.660 to 0.907, p = 0.002). Steroid treatment reduced mortality by 24% relative to no steroid treatment (RRR 0.24). These results support the use of glucocorticoids in COVID-19 in this subgroup of patients.
El síndrome por anticuerpos antisintetasa (SAS) es una entidad autoinmune que comprende la presencia de un anticuerpo antisintetasa (AAS), principalmente anti-Jo-1, anti-PL-7 y anti-PL-12 y al menos ...una de las siguientes características clínicas: miositis, enfermedad pulmonar intersticial –EPI-, artritis, fiebre, fenómeno de Raynaud y “manos de mecánico”. La rareza del síndrome y los pocos estudios al respecto hacen que aún existan múltiples interrogantes en torno a la etiopatogenia, tratamiento y pronóstico del mismo. Mediante la realización de cuatro estudios independientes, esta Tesis Doctoral intentará dar respuesta a varias de estas cuestiones.
En el primero se analiza las características clínicas de una cohorte de 59 pacientes con SAS, poniendo especial énfasis en la descripción y evolución de la EPI. Se analiza además la supervivencia de la cohorte, de manera global y por subgrupos, comparándola con las series publicadas. Los resultados muestran una alta frecuencia de EPI, pero sin poder confirmar que ésta sea un factor de mal pronóstico; los únicos factores que predicen una menor supervivencia son el descenso de la capacidad vital forzada (CVF) ≥ 10% durante el seguimiento y la presencia de hipertensión arterial pulmonar. La supervivencia global de la serie a los 5 y 10 años es del 83% y 80%. No se observan diferencias en cuanto a la supervivencia respecto a los pacientes con miositis sin AAS. Se objetiva una alta frecuencia de pericarditis especialmente en pacientes con anti-PL-7.
En el segundo estudio se analiza la exposición ocupacional en pacientes con SAS, y su relación con la presencia y evolución de la EPI. Los resultados muestran una alta exposición laboral (50%), más elevada que en la población de referencia y que en los pacientes con miositis sin AAS. El estudio sugiere que la exposición ambiental podría desempeñar un papel en la etiopatogenia del síndrome.
El tercer trabajo estudia la eficacia de los inhibidores de la calcineurina (IC) (ciclosporina y tacrólimus) en una serie de 15 pacientes con EPI asociada a SAS. Tras el seguimiento, 13 de ellos presentaron una mejoría y/o estabilización del funcionalismo pulmonar. Estos resultados indican que los IC podrían ser una buena opción terapéutica en los pacientes con SAS.
En el último trabajo, un estudio multicéntrico europeo, se describen las características clínicas y de laboratorio de una cohorte de 18 pacientes con anti-PL-7, y se comparar con las series publicadas previamente. Los resultados indican que tal y como ocurre con otros anticuerpos antisintetasa, la miositis y la EPI son manifestaciones frecuentes del SAS. El hallazgo de una alta prevalencia de pericarditis en estos pacientes (50%), no descrito hasta la fecha, implica que es posible que existan nuevas manifestaciones en estos pacientes.
En conclusión, los estudios muestran que la EPI es una manifestación frecuente que ocurre en casi el 80% de los casos de SAS, pero la existencia de la misma de por sí sola no implica un pronóstico negativo. El descenso ≥ 10% en la CVF y la presencia de hipertensión arterial pulmonar son datos asociados a una mayor mortalidad. La supervivencia acumulada a los 10 años es del 80%. Identificamos una alta prevalencia de exposición ocupacional en nuestra cohorte, la cual podría ser desencadenante del síndrome. Además de las características clínicas clásicas, objetivamos una alta prevalencia de pericarditis en los pacientes con anti-PL-7, un nuevo hallazgo que debería de ser estudiado. Finalmente, los IC deberían de ser considerados una buena opción terapéutica para el manejo de la EPI asociada al SAS.
Antisynthetase syndrome (ASS) is a rare autoimmune disorder that consists on a variety of clinical manifestations (myositis, interstitial lung disease –ILD- arthritis, fever, Raynaud´s phenomenon and “mechanic´s hands”) and the presence of an antisynthetase antibody (ASA), being the most common anti-Jo-1, anti-PL-12, anti-PL7. Due to the rarity of this syndrome, little is known about several aspects of the disease such as ethiopatogenic mechanisms, differences between autoantibodies and survival or mortality rates. This doctoral thesis, divided in four studies and based on a series of 59 patients with ASS, will try to answer some of these questions.
The aim of the first study is to describe and analyse the clinical characteristics of 59 patients with ASS, focusing on the ILD, and to analyse the survival of the series. Our results show that ILD is a major complication of the ASS, but its presence does not imply a bad prognosis. A more than 10% decrease in forced vital capacity (FVC) in the follow-up and the presence of pulmonary hypertension are the only two prognostic factors associated with lower survival rates. Cumulative survival at 5 and 10 years are 83 and 80% respectively, but no differences were found when compared with a group of patients with myositis without ASA. An unusually high frequency of pericarditis was assessed in patients with anti-PL-7 antibodies.
On the second study we investigate the occupational exposure in patients with ASS, finding a high occupational exposure (up to 50%), much higher of that in the reference population and in patients with myositis without ASA. This study suggests that occupational exposure could be implied in the onset and development of the ASS.
The third study analyses the effect of calcineurin inhibitors (CI) (cyclosporine and tacrolimus) in 15 patients with ASS associated ILD. A more than 10% increase in FVC was observed in 13 patients (80% refractory cases and 10% first-line therapy). Our study shows that CI are useful in the treatment o ASS associated ILD, not only in refractory cases but also as a first-line therapy.
In the last study, a European multicenter study (Eumyonet), we describe clinical and laboratory characteristics of a cohort of 18 European anti-PL-7 patients, and compare them to previously reported cases. All patients had myositis, and 56% had ILD. Interestingly, 50% of them showed pericarditis. Our results indicate that as in other subsets of ASS, myositis and ILD are common features of the anti-PL-7 AAS syndrome, and we should also add pericarditis as a possible manifestation related to anti-PL-7 antibodies.
In conclusion, our studies suggest that ASS is a heterogeneous syndrome. ILD is a common manifestation that occurs in up to 80% of the cases, but the poor prognosis depends not on its presence but on a decrease of more than 10% in FVC. Our results show that overall survival rates are better than those reported previously, with 80% of cumulative survival at 10 years. We identify a high occupational exposure rate in our patients, which could be a trigger in the development of the ASS. Apart from the classic clinical characteristics, we found a high prevalence of pericarditis in our anti-PL-7 patient series, a novel finding that should be further investigated. Finally, CI should be considered as good therapeutic option for managing ASS associated ILD.
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