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COPD patients are prone to acute infectious exacerbations that impair their quality of life and hamper prognosis. The purpose of the present study was to investigate the in situ IFN-β response in the lungs of stable COPD and non-COPD patients. Lung samples from 70 subjects (9 control never smokers, 19 control smokers without COPD, 21 patients with moderate COPD and 21 patients with very severe COPD) were studied for the expression of IFN-β, its main transcription factor, IRF-7, and two products of its autocrine function, namely RIG-I and MDA-5, by immunohistochemical techniques and quantitative real-time PCR. IFN-β, IRF-7, RIG-I and MDA-5 were widely detected in most lung cell types. In epithelial tissues and alveolar macrophages, IFN-β and IRF-7 labeling scores were decreased up to 65% and 74%, respectively, for COPD patients, paralleling an analogous reduction (43% and 65%, respectively) in the amount of their lung mRNA. Moreover, this decreased production of IFN-β in COPD patients correlated with a similar decrease in the expression of RIG-I and MDA-5, two essential members of the innate immune system. Our study indicates that most lung cells from stable COPD patients show a constitutive decreased expression of IFN-β, IRF-7, RIG-I and MDA-5, suggesting that this deficiency is the main cause of their acute viral exacerbations.

Poor sleep quality is frequent among COPD patients and it has been related to worse outcomes. The objective of this study was to compare the COPD and Asthma Sleep Impact Scale (CASIS) and the generic Pittsburgh Sleep Quality Index (PSQI) questionnaires as reliable tools for evaluating sleep quality and its relationship with COPD characteristics and survival. Stable COPD patients were prospectively evaluated. Anthropometric, sociodemographic, comorbidity, lung function and treatment data were collected. All patients completed CASIS and PSQI, mMRC dyspnea severity scale, COPD Assessment Test (CAT), sleep apnoea STOP-Bang and Hospital Anxiety and Depression Scale (HADS) questionnaires. Body mass index, airflow Obstruction, Dyspnea and Exacerbations (BODEx) index was calculated. Life status was determined after a mean follow-up of 3.7 (SD 1) years. We included 200 patients, 69.5% male, mean age 65.8 (9) years. Poor sleep was detected in 100 (50%) and 84 patients (42%) according to PSQI and CASIS questionnaires, respectively, with an agreement of 63%. Poor sleep was related to female gender, more severe dyspnea and worse BODEx, HADS and CAT scores according to both questionnaires. PSQI was associated to chronic pain or inferior urinary tract symptoms and CASIS to exacerbations, shorter walked distance in the 6-min walking test and treatment with oral corticosteroids or chronic oxygen. Thirty nine (19.5%) patients died during follow-up. Mortality was not associated to PSQI nor CASIS results. Unlike PSQI, CASIS is more related to COPD severity and its results are not influenced by comorbidities with known impact on sleep quality. In our sample, poor sleep quality was not associated with increased mortality.

We thank Dr Hoy and Dr Sim for their comments on our recent study.1 We wish to respond to three key points raised in their letter to the editor.2

Intra-atrial re-entrant tachycardia (IART) is a severe complication in patients with congenital heart disease (CHD). Cavotricuspid isthmus (CTI)-related IART is the most frequent mechanism. However, due to fibrosis and surgical scars, non-CTI-related IART is frequent. The main objective of this study was to describe the types of IART, circuit locations, and to analyze predictors of CTI versus non-CTI-related IART. This is an observational study that includes all consecutive patients with CHD who underwent a first IART ablation in a single referral tertiary hospital from January 2009 to December 2015 (94 patients; 39.4% women; age: 36.55 ± 14.9 years, 40.4% with highly complex cardiac disease). During the study, 114 IARTs were ablated (1.21 ± 0.41 IARTs per patient). CTI-related IART was the only arrhythmia in 51% (n = 48) of patients; non-CTI-related IART was the only mechanism in 27.7% (n = 26), and 21.3% of patients (n = 20) presented the two types of IART. Severe dilation of the systemic ventricle, absence of severe dilation of the venous atrium, highly complex cardiac defects, and nontypical electrocardiography (ECG) were related to non-CTI-related IART in univariate analysis. In multivariate analysis, nontypical ECG (odds ratio 3.64; 1.01 to 4.9; p = 0.049) and grade III CHD complexity (odds ratio 9.43; 1.44 to 11.7; p = 0.001) were predictors of non-CTI-related IART. In conclusion, in our population with a high proportion of complex CHD, CTI-related IART was the most frequent mechanism, although non-CTI-related IART was present in 49% (alone or with concomitant CTI-related IART). High-grade CHD complexity and nontypical ECG were strongly related to non-CTI IART.

The effectiveness of noninvasive respiratory support in severe COVID-19 patients is still controversial. We aimed to compare the outcome of patients with COVID-19 pneumonia and hypoxemic respiratory failure treated with high-flow oxygen administered via nasal cannula (HFNC), continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV), initiated outside the intensive care unit (ICU) in 10 university hospitals in Catalonia, Spain. We recruited 367 consecutive patients aged ≥ 18 years who were treated with HFNC (155, 42.2%), CPAP (133, 36.2%) or NIV (79, 21.5%). The main outcome was intubation or death at 28 days after respiratory support initiation. After adjusting for relevant covariates and taking patients treated with HFNC as reference, treatment with NIV showed a higher risk of intubation or death (hazard ratio 2.01; 95% confidence interval 1.32–3.08), while treatment with CPAP did not show differences (0.97; 0.63–1.50). In the context of the pandemic and outside the intensive care unit setting, noninvasive ventilation for the treatment of moderate to severe hypoxemic acute respiratory failure secondary to COVID-19 resulted in higher mortality or intubation rate at 28 days than high-flow oxygen or CPAP. This finding may help physicians to choose the best noninvasive respiratory support treatment in these patients. Clinicaltrials.gov identifier: NCT04668196.

Self-reported occupational exposure was previously associated with COPD in the Spanish population. This study aimed to analyse the relationship between occupational exposure to various chemical and biological agents, COPD, emphysema, and the bronchial wall area, which was determined by lung computed tomography (CT) in 226 individuals with COPD and 300 individuals without COPD. Lifetime occupational exposures were assessed using the ALOHA(+) job exposure matrix, and CT and spirometry were also performed. COPD was associated with high exposure to vapours, gases, dust and fumes (VGDF) (OR 2.25 95% CI 1.19–4.22), biological dust (OR 3.01 95% CI 1.22–7.45), gases/fumes (OR 2.49 95% CI 1.20–5.17) and with exposure to various types of solvents. High exposure to gases/fumes, chlorinated solvents and metals (coefficient 8.65 95% CI 1.21–16.09, 11.91 95%CI 0.46- 23.36, 14.45 95% CI 4.42–24.49, respectively) and low exposure to aromatic solvents (coefficient 8.43 95% CI 1.16–15.70) were associated with a low 15th percentile of lung density indicating emphysema. We conclude that occupational exposure to several specific agents is associated with COPD and emphysema in the Spanish population.

Background This study aims to (i) evaluate the association between anxiety and depressive symptoms and health-related quality of life (HRQoL); and (ii) identify the effect modifiers of this relationship in patients with chronic obstructive pulmonary disease (COPD). Methods A total of 337 clinically stable COPD patients answered the St. George's Respiratory Questionnaire (SGRQ) (assessing HRQoL) and the Hospital Anxiety and Depression Scale (HADS). Socio-demographic information, lung function, and other clinical data were collected. Results Most patients (93%) were male; they had a mean (SD) age of 68 (9) years and mild to very severe COPD (post-bronchodilator FEV 1 52 (16)% predicted). Multivariate analyses showed that anxiety, depression, or both conditions were associated with poor HRQoL (for all SGRQ domains). The association between anxiety and total HRQoL score was 6.7 points higher (indicating a worse HRQoL) in current workers than in retired individuals. Estimates for patients with \"both anxiety and depression\" were 5.8 points lower in stage I-II than in stage III-IV COPD, and 10.2 points higher in patients with other comorbidities than in those with only COPD. Conclusions This study shows a significant association between anxiety, depression, or both conditions and impaired HRQoL. Clinically relevant factors affecting the magnitude of this association include work status, COPD severity, and the presence of comorbidities.

The objective of the study is to report the contraceptive methods used by patients with congenital heart disease (CHD) before referral to a specific preconception clinic and evaluate safety and treatment adherence of the alternative contraception method, progesterone-only component (PC), offered. Contraceptive methods in the CHD population reported included estrogen-progesterone combined contraceptives (EPCC), despite the potential risk for thromboembolism. PC has been suggested as an alternative, but, no information on its use has been reported. Retrospective analysis was performed of all patients (n = 237) referred to the preconception clinic of an adult CHD center. Thirty-three percent of patients had used EPCC in the past; 3.8% had had thromboembolic events during its use. Current contraception consisted of barrier methods in 58% of patients, EPCC in 18%, and PC in 1.3%; 21.7% of patients were not using any contraception. PC was offered as an alternative in 146 patients; 73% of patients agreed to start the treatment. At a median follow-up of 1 year, 73% of patients who started PC maintained the treatment. Gynecologic side effects were reported in 25% of patients, with no cardiovascular effects. In conclusion, a significant proportion of patients with CHD were former users of EPCC, although some had formal contraindications, and the rate of PC use before referral to the preconception clinic was low. After being offered as an alternative treatment, the use of PC in its various forms was extensive, with no thrombogenic side effects and an acceptable rate of gynecologic side effects being reported.

Occupational exposure to dusts, gases and fumes has been associated with reduced FEV1 and sputum production in COPD patients. The effect of occupational exposure on other characteristics of COPD, especially those reflecting emphysema, has not been studied in these patients. We studied 338 patients hospitalized for a first exacerbation of COPD in 9 Spanish hospitals, obtaining full occupational history in a face-to-face interview; job codes were linked to a job exposure matrix for semi-quantitative estimation of exposure to mineral/biological dust, and gases/fumes for each job held. Patients underwent spirometry, diffusing capacity testing and analysis of gases in stable conditions. Quality of life, dyspnea and chronic bronchitis symptoms were determined with a questionnaire interview. A high- resolution CT scan was available in 133 patients. 94% of the patients included were men, with a mean age of 68(8.5) years and a mean FEV1% predicted 52 (16). High exposure to gases or fumes was associated with chronic bronchitis, and exposure to mineral dust and gases/fumes was associated with higher scores for symptom perception in the St. George's questionnaire. No occupational agent was associated with a lower FEV1. High exposure to all occupational agents was associated with better lung diffusion capacity, in long-term quitters. In the subgroup with CT data, patients with emphysema had 18% lower DLCO compared to those without emphysema. In our cohort of COPD patients, high exposure to gases or fumes was associated with chronic bronchitis, and high exposure to all occupational agents was consistently associated with better diffusion capacity in long-term quitters.

Alpha-1 antitrypsin deficiency (AATD) remains an underdiagnosed condition despite initiatives developed to increase awareness. The objective was to describe the current situation of the diagnosis of AATD in primary care (PC) in Catalonia, Spain. We performed a population-based study with data from the Information System for Development in Research in Primary Care, a population database that contains information of 5.8 million inhabitants (80% of the population of Catalonia). We collected the number of alpha-1 antitrypsin (AAT) determinations performed in the PC in two periods (2007-2008 and 2010-2011) and described the characteristics of the individuals tested. A total of 12,409 AAT determinations were performed (5,559 in 2007-2008 and 6,850 in 2010-2011), with 10.7% of them in children. As a possible indication for AAT determination, 28.9% adults and 29.4% children had a previous diagnosis of a disease related to AATD; transaminase levels were above normal in 17.7% of children and 47.1% of adults. In total, 663 (5.3%) individuals had intermediate AATD (50-100 mg/dL), 24 (0.2%) individuals had a severe deficiency (<50 mg/dL), with a prevalence of 0.19 cases of severe deficiency per 100 determinations. Nine (41%) of the adults with severe deficiency had a previous diagnosis of COPD/emphysema, and four (16.7%) were diagnosed with COPD within 6 months. The number of AAT determinations in the PC is low in relation to the prevalence of COPD but increased slightly along the study period. The indication to perform the test is not always clear, and patients detected with deficiency are not always referred to a specialist.