Management of progressive pulmonary fibrosis associated with connective tissue disease

Introduction: Fibrotic interstitial lung disease (ILD) is a frequent and severe complication of connective tissue disease (CTD). Areas covered: In this narrative review, we update the most relevant differential characteristics of fibrotic ILD associated with CTD (CTD-ILD) and propose a diagnostic and therapeutic approach based on a review of the articles published between 2002 and 2022 through PubMed. Expert opinion: The subset of ILD, mainly the radiological/histological pattern and the degree of fibrotic component, usually determines the prognosis and therapeutic strategy for these patients. Some patients with CTD-ILD can develop progressive pulmonary fibrosis (PPF) with severe deterioration of lung function, rapid progression to chronic respiratory failure, and high mortality. PPF has been described in many CTDs, mainly in systemic sclerosis and rheumatoid arthritis, and requires a multidisciplinary diagnostic and therapeutic approach to improve patient outcomes

Diagnostic delay of associated interstitial lung disease increases mortality in rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main extra-articular organ affected is the lung, sometimes in the form of diffuse interstitial lung disease (ILD) and conditions the prognosis. A multicenter, observational, descriptive and cross-sectional study of consecutive patients diagnosed with RA-ILD. Demographic, analytical, respiratory functional and evolution characteristics were analyzed to evaluate the predictors of progression and mortality. 106 patients were included. The multivariate analysis showed that the diagnostic delay was an independent predictor of mortality (HR 1.11, CI 1.01-1.23, p = 0.035). Also, age (HR 1.33, 95% CI 1.09-1.62, p = 0.0045), DLCO (%) (HR 0.85, 95% CI 0.73-0.98, p = 0.0246), and final SatO2 (%) in the 6MWT (HR 0.62, 95% CI 0.39-0.99, p = 0.0465) were independent predictor variables of mortality, as well as GAP index (HR 4.65, 95% CI 1.59-13.54, p = 0.0051) and CPI index (HR 1.12, 95% CI 1.03-1.22, p = 0.0092). The withdrawal of MTX or LFN after ILD diagnosis was associated with disease progression in the COX analysis (HR 2.18, 95% CI 1.14-4.18, p = 0.019). This is the first study that highlights the diagnostic delay in RA-ILD is associated with an increased mortality just like happens in IPF

Causes of Pulmonary Fibrosis in the Elderly

Idiopathic pulmonary fibrosis (IPF) is the most common and most lethal type of idiopathic interstitial pneumonia. It is a chronic, aging-associated lung disease characterized by fibrotic foci and inflammatory infiltrates, with no cure and very limited therapeutic options. Although its etiology is unknown, several pathogenic pathways have been described that could explain this process, involving aging, environmental factors, genomic instability, loss of proteostasis, telomere attrition, epigenetic changes, mitochondrial dysfunction, cell senescence, and altered intercellular communication. One of the main prognostic factors for the development of IPF in broad epidemiological studies is age. The incidence increases with age, making this a disease that predominantly affects the elderly population, being exceptional under 45 years of age. However, the degree to which each of these mechanisms is involved in the etiology of the uncontrolled fibrogenesis that defines IPF is still unknown. Clarifying these questions is crucial to the development of points of intervention in the pathogenesis of the disease. This review briefly summarizes what is known about each possible etiological factor, and the questions that most urgently need to be addressed

El comienzo del cambio de tendencia en las tasas de mortalidad por cáncer de pulmón en España, 1980-2018

[EN]: [Background]: Recently, some countries have shown stable trends in lung cancer death rates among women not yet described for Spain. We propose to update lung cancer mortality rates in Spain during the period of 1980–2018 by sex and region. [Methods]: We used lung cancer mortality (International Classification of Diseases code 162 for the 9th edition, and codes C33 and C34 for 10th edition) and population data from the Spanish National Statistics Institute for the period 1980–2018. Age-standardised mortality rates (ASMRs), all ages and 30–64 years, by region and sex were assessed through joinpoint regression. [Results]: During the study period lung cancer ASMRs (all ages) in men decreased -0.4% per annum and increased by 3.1% in women. Recently, ASMR (30–64 years) accelerated its decrease (1992–2007; −0.7 and 2007–2018; −3.5%) in men and slowed its increase (1990–2012; 5.7% and 2012–2018; 1.4%) in women. In men, joinpoint analysis detected an initial period in all Autonomous Communities (ACs) in which the rates significantly increased, followed by a second period in which the rates decreased significantly (12 ACs) or remained stable (4 ACs) since the late 1980s or early 1990s. In women, upward trends in ASMRs (all ages) were observed for the whole period in all the ACs. In 13 ACs, an initial period was detected with joinpoint in which the rates remained stable or significantly decreased, followed by a second period in which the rates increased significantly since the late 1980s or early 1990s. [Conclusions]: Our study shows gender differences in lung cancer mortality trends in Spain. These differences may be explained by the increased use of tobacco among women and the decreased use among men.[ES]: [Antecedentes]: Recientemente, algunos países han mostrado tendencias estables en las tasas de mortalidad por cáncer de pulmón entre las mujeres que aún no se han descrito para España. Proponemos actualizar las tasas de mortalidad por cáncer de pulmón en España durante el período 1980-2018 por sexo y región. [Métodos]: Utilizamos la mortalidad por cáncer de pulmón (código 162 de la Clasificación Internacional de Enfermedades según la novena edición, y los códigos C33 y C34 según la décima edición) y los datos poblacionales del Instituto Nacional de Estadística de España para el período 1980-2018. Las tasas específicas de mortalidad por edad (TEME), para todas las edades y entre los 30 y 64 años, por región y sexo, se evaluaron mediante el análisis de regresión por segmentos. [Resultados]: Durante el período de estudio, la TEME (todas las edades) de cáncer de pulmón disminuyó un −0,4% por año en hombres y aumentó un 3,1% en mujeres. Recientemente, la TEME (30-64 años) aceleró su descenso (1992-2007: −0,7% y 2007-2018: −3,5%) en los hombres y desaceleró su aumento (1990-2012: 5,7% y 2012-2018: 1,4%) en las mujeres. En los hombres, el análisis de regresión por segmentos detectó un período inicial en todas las comunidades autónomas (CA) en el que las tasas aumentaron significativamente, seguido de un segundo período en el que las tasas disminuyeron significativamente (12 CA) o se mantuvieron estables (4 CA) desde finales de la década de los ochenta o principios de los noventa. En las mujeres, las tendencias al alza en la TEME (todas las edades) se observaron durante todo el período en todas las CA. En 13 CA, se detectó con el análisis de regresión un período inicial en el que las tasas se mantuvieron estables o disminuyeron significativamente, seguido de un segundo período en el que las tasas aumentaron significativamente desde finales de los años ochenta o principios de los noventa. [Conclusiones]: Nuestro estudio muestra diferencias de género en las tendencias de mortalidad por cáncer de pulmón en España. Estas diferencias pueden explicarse por el aumento del uso de tabaco en las mujeres y la disminución del uso entre los hombres

Impact of high-flow oxygen therapy during exercise in idiopathic pulmonary fibrosis: a pilot crossover clinical trial

Background: Supplemental oxygen delivered with standard oxygen therapy (SOT) improves exercise capacity in patients with idiopathic pulmonary fibrosis (IPF). Although high-flow nasal cannula oxygen therapy (HFNC) improves oxygenation in other respiratory diseases, its impact on exercise performance has never been evaluated in IPF patients. We hypothesized that HFNC may improve exercise capacity in IPF subjects compared to SOT. Methods: This was a prospective, crossover, pilot randomized trial that compared both oxygenation methods during a constant submaximal cardiopulmonary exercise test (CPET) in IPF patients with exertional oxygen saturation (SpO2) ≤ 85% in the 6-min walking test. The primary outcome was endurance time (Tlim). Secondary outcomes were muscle oxygen saturation (StO2) and respiratory and leg symptoms. Results: Ten IPF patients [71.7 (6) years old, 90% males] were included. FVC and DLCO were 58 ± 11% and 31 ± 13% pred. respectively. Tlim during CPET was significantly greater using HFNC compared to SOT [494 ± 173 vs. 381 ± 137 s, p = 0.01]. HFNC also associated with a higher increase in inspiratory capacity (IC) [19.4 ± 14.2 vs. 7.1 ± 8.9%, respectively; p = 0.04], and a similar trend was observed in StO2 during exercise. No differences were found in respiratory or leg symptoms between the two oxygen devices. Conclusions: This is the first study demonstrating that HFNC oxygen therapy improves exercise tolerance better than SOT in IPF patients with exertional desaturation. This might be explained by changes in ventilatory mechanics and muscle oxygenation. Further and larger studies are needed to confirm the benefits of HFNC in IPF patients and its potential usefulness in rehabilitation programs