Antibody responses and risk factors associated with impaired immunological outcomes following two doses of BNT162b2 COVID-19 vaccination in patients with chronic pulmonary diseases.

INTRODUCTION: Responses to COVID-19 vaccination in patients with chronic pulmonary diseases are poorly characterised. We aimed to describe humoral responses following two doses of BNT162b2 mRNA COVID-19 vaccine and identify risk factors for impaired responses. METHODS: Prospective cohort study including adults with chronic pulmonary diseases and healthcare personnel as controls (1:1). Blood was sampled at inclusion, 3 weeks, 2 and 6 months after first vaccination. We reported antibody concentrations as geometric means with 95% CI of receptor binding domain (RBD)-IgG and neutralising antibody index of inhibition of ACE-2/RBD interaction (%). A low responder was defined as neutralising index in the lowest quartile (primary outcome) or RBD-IgG <225 AU/mL plus neutralising index <25% (secondary outcome), measured at 2 months. We tested associations using Poisson regression. RESULTS: We included 593 patients and 593 controls, 75% of all had neutralising index ≥97% at 2 months. For the primary outcome, 34.7% of patients (n=157/453) and 12.9% of controls (n=46/359) were low responders (p<0.0001). For the secondary outcome, 8.6% of patients (n=39/453) and 1.4% of controls (n=5/359) were low responders (p<0.001). Risk factors associated with low responder included increasing age (per decade, adjusted risk ratio (aRR) 1.17, 95% CI 1.03 to 1.32), Charlson Comorbidity Index (per point) (aRR 1.15, 95% CI 1.05 to 1.26), use of prednisolone (aRR 2.08, 95% CI 1.55 to 2.77) and other immunosuppressives (aRR 2.21, 95% CI 1.65 to 2.97). DISCUSSION: Patients with chronic pulmonary diseases established functional humoral responses to vaccination, however lower than controls. Age, comorbidities and immunosuppression were associated with poor immunological responses.

Aspergilloma complicating previous COVID-19 pneumonitis - a case report.

Aspergillomas are found in pre-existing cavities in pulmonary parenchyma. To the best of our knowledge, aspergilloma has not previously been reported in COVID-19-associated pulmonary architecture distortion combined with barotrauma from invasive mechanical ventilation therapy. We present a case of a 67-year-old woman, who suffered from severe COVID-19 in the summer of 2020 with no suspicion of infection with Aspergillus in the acute phase. Ten months after discharge from her COVID-related admission, she developed bilateral aspergillomas diagnosed by image diagnostics, bronchoscopy, and blood samples, and she now receives antifungal therapy. We would like to raise awareness on aspergilloma in post-COVID-19 patients, since it is an expected long-term complication to COVID-19 patients with pulmonary architectural distortion.

Predictors of COPD in symptomatic smokers and ex-smokers seen in primary care.

Even in subjects at high risk of chronic obstructive pulmonary disease (COPD), the diagnosis is often missed due to lack of awareness of symptoms and risk factors. The objective of this study was to identify predictors of a diagnosis of COPD in symptomatic current and ex-smokers seen in a primary care setting. General practitioners ( n = 241) consecutively recruited subjects ≥ 35 years, with tobacco exposure, at least one respiratory symptom (i.e. cough, sputum, wheeze, dyspnoea and/or recurrent lower respiratory tract infections), and no previous diagnosis of obstructive airways disease. Information on age, smoking status, body mass index (BMI) and dyspnoea (Medical Research Council (MRC) dyspnoea scale) was obtained. Individuals with airway obstruction (i.e. forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio (FVC) < 0.70) at initial spirometry had a diagnostic spirometry after administration of a bronchodilator. COPD was defined as the presence of symptoms, tobacco exposure and persistent airflow limitation. The most prevalent symptoms were cough (72%) and dyspnoea (48%). Of 3875 (50% females, mean age 57 years) subjects screened, 700 (18.1%) were diagnosed with COPD. Multivariate logistic regression analysis revealed that increasing age 50-59 years (OR 2.4, 95% CI 1.8-3.3), 60-69 years (OR 4.1, 95% CI 3.1-5.5), ≥70 years (OR 5.7, 95% CI 4.2-7.8), BMI < 25 (OR 2.3, 95% CI 1.9-2.7), being current smoker (OR 1.2, 95% CI 1.01-1.5), self-reported dyspnoea (OR 1.7, 95% CI 1.4-2.0), wheeze (OR 1.9, 95% CI 1.5-2.3) and sputum (OR 1.4, 95% CI 1.1-1.7) were associated with a significantly higher risk of being diagnosed with COPD. No association was found between gender, cough and recurrent respiratory tract infections and a diagnosis of COPD. Among symptomatic smokers and ex-smokers seen in primary care, self-reported sputum production, wheeze, dyspnoea and low BMI identify a subgroup with a higher likelihood of COPD.

Multicenter study of the COPD-6 screening device: feasible for early detection of chronic obstructive pulmonary disease in primary care?

BACKGROUND AND AIM: Early detection of COPD may reduce the future burden of the disease. We aimed to investigate whether prescreening with a COPD-6 screening device (measuring FEV1 and FEV6) facilitates early detection of COPD in primary care. METHODS: In primary care, individuals at high risk of COPD (ie, age ≥35 years, relevant exposure, and at least one respiratory symptom) and no previous diagnosis of obstructive lung disease were examined with a COPD-6 screening device. In prioritized order, the criteria for proceeding to confirmatory spirometry were FEV1/FEV6 <0.7, FEV1 <80%pred, or clinical suspicion of COPD regardless of test result (medical doctor's [MD] decision). Based on spirometry, including bronchodilator (BD) reversibility test, individuals were classified as COPD (post-BD FEV1/FVC <0.70), asthma (ΔFEV1 ≥0.50 L), or no obstructive lung disease. RESULTS: A total of 2,990 subjects (54% men, mean age 59 years, and mean 28 pack-years) were enrolled, of whom 949 (32%) proceeded from COPD-6 screening to confirmative spirometry based on the following criteria: 510 (54%) FEV1/FEV6 <0.70, 382 (40%) FEV1 <80%pred, and 57 (6%) MD decision. Following confirmative spirometry, the 949 individuals were diagnosed as having COPD (51%), asthma (3%), and no obstructive lung disease (45%). COPD was diagnosed in 487 (16%) of the enrolled subjects in whom confirmative spirometry was performed in 69% based on FEV1/FEV6 <0.7 and in 29% based on FEV1 ≤80%pred. CONCLUSION: Prescreening with the COPD-6 device showed acceptable specificity for the selection of subjects for diagnostic spirometry and is likely to be a useful alternative to current practice in primary care.

Identifying possible asthma-COPD overlap syndrome in patients with a new diagnosis of COPD in primary care.

The asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) remains poorly characterised. Our aim was to describe an algorithm for identifying possible ACOS in adults with newly diagnosed COPD in primary care. General practitioners (n=241) consecutively recruited subjects ⩾35 years, with tobacco exposure, at least one respiratory symptom and no previous diagnosis of obstructive lung disease. Possible ACOS was defined as chronic airflow obstruction, i.e., post-bronchodilator (BD) forced expiratory volume 1/forced vital capacity (FEV1/FVC) ratio<0.70, combined with wheeze (ACOS wheeze) and/or significant BD reversibility (ACOS BD reversibility). Of 3,875 (50% females, mean age 57 years) subjects screened, 700 (18.1%) were diagnosed with COPD, i.e., symptom(s), tobacco exposure and chronic airflow obstruction. Indications for ACOS were found in 264 (38%) of the COPD patients. The prevalence of ACOS wheeze and ACOS BD reversibility was 27% (n=190) and 16% (n=113), respectively (P<0.001), and only 6% (n=39) of the COPD patients fulfilled both criteria for ACOS. Patients with any ACOS were younger (P=0.04), had more dyspnoea (P<0.001), lower FEV1%pred (67% vs. 74%; P<0.001) and lower FEV1/FVC ratio (P=0.001) compared with COPD-only patients. Comparing subjects fulfilling both criteria for ACOS with those fulfilling criteria for ACOS wheeze only (n=151) and those fulfilling criteria for ACOS BD reversibility only (n=74) revealed no significant differences. Irrespective of the applied ACOS definition, no significant difference in life-time tobacco exposure was found between ACOS- and COPD-only patients. In subjects with a new diagnosis of COPD, the prevalence of ACOS is high. When screening for COPD in general practice among patients with no previous diagnosis of obstructive lung disease, patients with possible ACOS may be identified by self-reported wheeze and/or BD reversibility.

Detection of COPD in a high-risk population: should the diagnostic work-up include bronchodilator reversibility testing?

BACKGROUND: Underdiagnosis of chronic obstructive pulmonary disease (COPD) is widespread. Early detection of COPD may improve the outcome by timely smoking cessation, a change in lifestyle, and treatment with an inhaled bronchodilator (BD). The objective of this study was to evaluate the diagnostic role of BD reversibility testing in early COPD case finding. METHODS: General practitioners (n=241) consecutively recruited subjects aged ≥35 years with relevant exposure (history of smoking, and/or occupational exposure) and at least one respiratory symptom. Information on age, smoking status, body mass index, dyspnea score (Medical Research Council scale), and spirometry was obtained. Individuals with airway obstruction (forced expiratory volume in one second [FEV1]/forced vital capacity [FVC] <0.70) underwent a BD test with an inhaled ß2 agonist, which was considered positive if ΔFEV1 was >0.20 L and >12%. Asthma and COPD were, respectively, defined as an FEV1 increase >0.50 L and a post-BD FEV1/FVC <0.70. RESULTS: In total, 4,049 subjects (51% male) were included (mean age 58 years, body mass index 27, 32 pack-years of smoking). A significant BD response was found in 143 (15%) of the 937 subjects (23%) with airway obstruction at screening spirometry. In 59% of these subjects, the post-BD FEV1/FVC remained <0.70. In 24% of the subjects with pre-BD airway obstruction, the post-BD FEV1/FVC ratio was within the reference range. In subjects with confirmed COPD, the mean increase in FEV1 following BD was 0.11 L±0.10 L. The subjects with COPD and a significant BD response were characterized by a higher prevalence of dyspnea (72% versus 57%, P=0.02) but less cough (55% versus 75%, P=0.001) when compared with COPD subjects without BD reversibility. CONCLUSION: Administration of a BD in COPD case finding is important in order to determine the post-BD FEV1/FVC ratio. Exclusion of subjects with a significant BD response may result in underdiagnosis of COPD, and we question the need for the BD reversibility test in the diagnostic screening algorithm in early COPD case finding.

[Oxygen therapy in exercise-induced hypoxemia improves physical capacity and reduces dyspnea in patients with COPD]. / Samtidig iltbehandling ved anstrengelsesudløst hypoksæmi forbedrer den fysiske formåen og reducerer åndenød hos patienter med KOL.

Many chronic obstructive pulmonary disease patients suffer from dyspnoea and reduced physical abilities. Some of the patients exhibit desaturation during physical exercise. Few studies have examined if oxygen therapy during physical exercise can relieve symptoms and improve outcomes of pulmonary rehabilitation. These studies show that oxygen therapy during exercise results in significant improvement in exercise capacity. Yet it is not possible to draw a clear conclusion regarding the effects of more prolonged (weeks) treatment. The studies are in general small and of poor methodological quality.