Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project.

BACKGROUND: The PI*S variant is one of the most prevalent mutations within alpha-1 antitrypsin deficiency (AATD). The risk of developing AATD-related lung disease in individuals with the PI*SS genotype is poorly defined despite its substantial prevalence. Our study aimed to characterize this genotype and its risk for lung disease and compare it with the PI*ZZ and PI*SZ genotypes using data from the European Alpha-1 antitrypsin Deficiency Research Collaboration international registry. METHOD: Demographic, clinical, functional, and quality of life (QoL) parameters were assessed to compare the PI*SS characteristics with the PI*SZ and PI*ZZ controls. A propensity score with 1:3 nearest-neighbour matching was performed for the most important confounding variables. RESULTS: The study included 1007 individuals, with PI*SS (n = 56; 5.6%), PI*ZZ (n = 578; 57.4%) and PI*SZ (n = 373; 37.0%). The PI*SS population consisted of 58.9% men, with a mean age of 59.2 years and a mean FEV1(% predicted) of 83.4%. Compared to PI*ZZ individuals they had less frequent lung disease (71.4% vs. 82.2%, p = 0.037), COPD (41.4% vs. 60%, p = 0.002), and emphysema (23.2% vs. 51.9%, p < 0.001) and better preserved lung function, fewer exacerbations, lower level of dyspnoea, and better QoL. In contrast, no significant differences were found in the prevalence of lung diseases between PI*SS and PI*SZ, or lung function parameters, exacerbations, dyspnoea, or QoL. CONCLUSIONS: We found that, as expected, the risk of lung disease associated with the PI*SS genotype is significantly lower compared with PI*ZZ, but does not differ from that observed in PI*SZ individuals, despite having higher serum AAT levels. TRIAL REGISTRATION: www. CLINICALTRIALS: gov (ID: NCT04180319).

Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. METHODS: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 µM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. RESULTS: A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). CONCLUSIONS: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registration www. CLINICALTRIALS: gov (ID: NCT04180319).

Hypersensitivity pneumonitis: application of a new diagnostic algorithm to a time series of the disease.

BACKGROUND: The diagnostic criteria for Hypersensitivity pneumonitis (HP) have changed over time. Our aim is to apply a recent diagnostic algorithm to a historical series of patients diagnosed with HP to assess its distribution according to current diagnostic criteria and the diagnostic confidence achieved. RESEARCH DESIGN AND METHODS: Application to each patient the algorithm criteria. The diagnosis was HP (≥90%), provisional high (70-89%) or low confidence (51-69%) or non-HP (unlikely) (≤50%); or HP, provisional or non-HP, if they had lung biopsy. RESULTS: 129 patients [mean age 64 ± 12 years; 79 (61.2%) women] were included of which 16 (12.4%) were diagnosed on the basis of high clinical suspicion. After applying the algorithm, 106 patients (82.2%) could be evaluated and 83 (78.3%) had a diagnosis of HP or high confidence. Lung biopsy was able to establish a diagnosis of certainty in another 21 patients and a provisional diagnosis in 9 more [total, 113 (87.6%)]. The 16 patients without strict diagnostic criteria for HP had a low confidence diagnosis. A total of 56 lung biopsies (64.4%) could have been avoided according to the new guidelines. CONCLUSIONS: The application of this algorithm achieves a high diagnostic yield in HP, significantly reducing the number of lung biopsies required.

Analysis of the quality of e-Consultations in chronic obstructive pulmonary disease.

INTRODUCTION: The quality of e-Consultations in the COPD is unknown. The objectives of this study were (i) to evaluate the quality of referrals; (ii) to define the characteristics of patients referred from Primary Care (PC) to the Unit of Pulmonology; and (iii) to describe differences between accepted and rejected patients. METHODS: A retrospective, observational study of e-Consultations requested by PC for suspected COPD throughout 2022. To quantify the quality of the e-Consultations, an arbitrary scale of 12 variables (score 0-10) was created. RESULTS: In total, 384 e-Consultations were reviewed, of which 167 (43.5 %) resulted in a face-to-face visit, and 217 (56.5 %) were rejected. No differences were observed between the two types of patients, except for confirmations of diagnostic suspicion of COPD [significantly higher in accepted patients (p = 0.042)]; physical examination data of rejected patients (more data provided; p = 0.015); and lung function (significantly better in rejected patients). The mean quality of referrals was acceptable (5.6 ± 2.1 score): 121 (31.3 %) had insufficient quality; 118 (30.5 %) acceptable; 75 (19.4 %) good, and 30 (7.8 %) excellent. Quality was low in half of the variables analyzed (6/12); acceptable in 3, and good in another 3. The capacity of resolution of referrals was good (one e-Consultation) in 199 requests (66.1 %); deficient (two e-Consultations) in 72 (23.9 %), and poor (≥3 e-Consultations) in 30 (10 %). Overdiagnosis was 40.2 % (86/214 e-Consultations). The risk could be classified in 247 patients (64.3 %; 135 low-risk; 90 high-risk). CONCLUSIONS: When adequate information is provided, e-Consultations help identify different levels of severity. However, the quality and capacity of resolution of referrals were suboptimal, with a high percentage of overdiagnoses.

A pulmonary rehabilitation program reduces hospitalizations in chronic obstructive pulmonary disease patients: A cost-effectiveness study.

BACKGROUND: Although pulmonary rehabilitation (PR) is recommended in patients with chronic obstructive pulmonary disease (COPD), there is a scarcity of data demonstrating the cost-effectiveness and effectiveness of PR in reducing exacerbations. METHODS: A quasi-experimental study in 200 patients with COPD was conducted to determine the number of exacerbations 1 year before and after their participation in a PR program. Quality of life was measured using the COPD assessment test and EuroQol-5D. The costs of the program and exacerbations were assessed the year before and after participation in the PR program. The incremental cost-effectiveness ratio (ICER) was estimated in terms of quality-adjusted life years (QALYs). RESULTS: The number of admissions, length of hospital stay, and admissions to the emergency department decreased after participation in the PR program by 48.2%, 46.6%, and 42.5%, respectively (P < 0.001 for all). Results on quality of life tests improved significantly (P < 0.001 for the two tests). The cost of PR per patient and the cost of pre-PR and post-PR exacerbations were €1867.7 and €7895.2 and €4201.9, respectively. The PR resulted in a cost saving of €1826 (total, €365,200) per patient/year, and the gain in QALYs was+0.107. ICER was -€17,056. The total cost was <€20,000/QALY in 78% of patients. CONCLUSIONS: PR contributes to reducing the number of exacerbations in patients with COPD, thereby slowing clinical deterioration. In addition, it is cost-effective in terms of QALYs.

Clinical characteristics of chronic obstructive pulmonary disease in never-smokers: A systematic review.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is the third cause of death worldwide. While tobacco smoking is a key risk factor, COPD also occurs in never-smokers (NS). However, available evidence on risk factors, clinical characteristics, and natural history of the disease in NS is scarce. Here, we perform a systematic review of the literature to better describe the characteristics of COPD in NS. METHODS: We searched different databases following the PRISMA guidelines with explicit inclusion and exclusion criteria. A purpose-designed quality scale was applied to the studies included in the analysis. It was not possible to pool the results due to the high heterogeneity of the studies included. RESULTS: A total of 17 studies that met the selection criteria were included, albeit only 2 of them studied NS exclusively. The total number of participants in these studies were 57,146 subjects, 25,047 of whom were NS and 2,655 of the latter had NS-COPD. Compared to COPD in smokers, COPD in NS is more frequent in women and older ages, and is associated with a slightly higher prevalence of comorbidities. There are not enough studies to understand if COPD progression and clinical symptoms in NS are different to that of ever-smokers. CONCLUSIONS: There is a significant knowledge gap on COPD in NS. Given that COPD in NS account for about a third of all COPD patients in the world, particularly in low-middle income countries, and the decrease in tobacco consumption in high income countries, understanding COPD in NS constitutes a public-health priority.

Risk factors for chronic obstructive pulmonary disease in never-smokers: A systematic review.

INTRODUCTION: Relatively little is known about the risk factors for chronic obstructive pulmonary disease (COPD) in never-smokers, and these factors have not yet been fully characterised. This study therefore sought to analyse COPD risk factors in never-smokers by conducting a systematic review of the literature on the topic. MATERIALS AND METHODS: We performed a search in PubMed (Medline) and Embase from 2000 onwards, to locate studies on COPD in never-smokers. For literature search and evidence synthesis purposes, we used the PRISMA guidelines and drew up a specific quality scale to quantify the evidence of each study included. RESULTS: The bibliographic search retrieved a total of 557 papers, 20 of which fulfilled the designated inclusion criteria (two case-control studies, four cohort studies and 14 cross-sectional studies). These studies were undertaken in Europe, the United States, Latin America, Asia and Africa. The risk factors for never-smokers were varied and ranged from exposure to biomass, occupational exposure and passive smoking to having a history of asthma, tuberculosis or respiratory infections during childhood. The effect of residential radon was unclear. The highest risk was obtained for previous respiratory diseases of any type, with a magnitude much higher than that observed for other risk factors. CONCLUSIONS: There are few studies on COPD risk factors in never-smokers. More purpose-designed studies in this subpopulation are thus called for, including well-designed studies to specifically assess if indoor radon has any role on COPD onset.

Response to inhaled ceftazidime in patients with non-cystic fibrosis bronchiectasis and chronic bronchial infection unrelated to Pseudomonas aeruginosa.

INTRODUCTION: Inhaled antibiotics reduce the frequency of exacerbations. The objective was to assess the efficacy of inhaled ceftazidime in patients with non-cystic fibrosis bronchiectasis (NCFB) and concomitant chronic bronchial infection (CBI) caused by potentially pathogenic microorganisms (PPM) other than Pseudomonas aeruginosa (PA). MATERIAL AND METHOD: Quasi-experimental study in 21 patients with exacerbations who developed CBI by a PPM other than PA. RESULTS: Bacterial infection was resolved in 85.7% patients. Rehospitalizations, length of hospital stay, moderate exacerbations and blood levels of CRP decreased significantly. In addition, SGRQ questionnaire also decreased more than 4 points in 57.1% of the patients. CONCLUSION: The results suggest that inhaled ceftazidime in NCFB unrelated to PA is a plausible alternative to the standard therapies used in clinical practice.

Cost-Effectiveness of a New Outpatient Pulmonology Care Model Based on Physician-to-Physician Electronic Consultation.

Introduction: This study assesses the impact of an electronic physician-to-physician consultation program on the waiting list and the costs of a Pulmonology Unit. Materials and Methods: A prepost intervention study was conducted after a new ambulatory pulmonary care protocol was implemented and the capacity of the unit was adopted. In the new model, physicians at all levels of healthcare send electronic consultations to specialists. Results: In the preintervention year (2019), the Unit of Pulmonology attended 7,055 consultations (466 e-consultations and 6,589 first face-to-face visits), which decreased to 6,157 (3,934 e-consultations and 2,223 first face-to-face visits; 12.7% reduction) in the postintervention year (all were e-consultations). The mean wait time for the first appointment was 25.7 days in 2019 versus 3.2 days in 2021 (p < 0.001). In total, 43.5% of cases were solved via physician-to-physiciane-consultation. A total of 2,223 patients needed a face-to-face visit, with a mean wait time of 7.5 days. The mean of patients in the waiting listing decreased from 450.8 in 2019 to 44.8 in 2021 (90% reduction). The annual time devoted to e-consultations and first face-to-face visits following an e-consultation diminished significantly after the intervention (1,724 hours versus 2,312.8; 25.4% reduction). Each query solved via e-consultation represented a saving of €652.8, resulting in a total annual saving of €827,062. Conclusions: Physician-to-physiciane-consultations reduce waiting times, improve access of complex patients to specialty care, and ensure that cases are managed at the appropriate level. E-consultation reduces costs, which benefits both, society and the healthcare system.

Health Outcomes: Towards the Accreditation of Respiratory Medicine Departments. / Resultados de salud: hacia la acreditación de los servicios de neumología.

National health systems must ensure compliance with conditions such as equity, efficiency, quality, and transparency. Since it is the right of society to know the health outcomes of its healthcare system, our aim was to develop a proposal for the accreditation of respiratory medicine departments in terms of care, teaching, and research, measuring health outcomes using quality of care indicators. The management tools proposed in this article should be implemented to improve outcomes and help us achieve our objectives. Promoting accreditation can serve as a stimulus to improve clinical management and enable professionals to take on greater leadership roles and take action to improve outcomes in patient care.

Efficacy of mepolizumab in usual clinical practice and characteristics of responders.

BACKGROUND: Severe eosinophilic asthma is a high-burden disease. Mepolizumab has been effective in several randomized clinical trials. However, such success might not be applicable to patients treated in usual clinical practice. The objectives of this article are to evaluate the efficacy of mepolizumab in severe uncontrolled eosinophilic asthma under usual clinical practice, and to determine characteristics associated with the response to this treatment. METHODS: We have conducted a retrospective, multicentre study, including all adult patients with severe uncontrolled eosinophilic asthma in Galicia, Spain, on whom mepolizumab treatment was started before June 2020, at least 6 months before the time of inclusion, and had received at least one dose of the drug. Patient characteristics, clinical data, respiratory function and comorbidities were collected at baseline and at the 6-month-follow-up. Responders and super-responders were defined according to clinical response and requirement of systemic corticosteroids. RESULTS: 122 patients (mean age 58 years old) were included. In the follow-up treatment 6 months later, 75.4% of the patients were well-controlled, displaying a significant reduction in blood eosinophil counts (p < 0.001), hospital admissions and disease exacerbations (p < 0.001), and had their systemic glucocorticosteroid dose significantly reduced (p < 0.001). The inhaled corticosteroid dose was also lowered (p < 0.01) after 6 months of treatment. Around two-thirds had a clinically significant increase in FEV1, 95% of the patients were considered responders and 43% super-responders. CONCLUSION: In routine clinical practice, mepolizumab is effective in patients with severe eosinophilic asthma and it has a good safety profile.

Health outcomes: Towards the accreditation of respiratory medicine departments.

National health systems must ensure compliance with conditions such as equity, efficiency, quality, and transparency. Since it is the right of society to know the health outcomes of its healthcare system, our aim was to develop a proposal for the accreditation of respiratory medicine departments in terms of care, teaching, and research, measuring health outcomes using quality of care indicators. The management tools proposed in this article should be implemented to improve outcomes and help us achieve our objectives. Promoting accreditation can serve as a stimulus to improve clinical management and enable professionals to take on greater leadership roles and take action to improve outcomes in patient care.

Common errors in inhalation therapy: Impact and solutions.

OBJECTIVE: Inhalation therapy is one of the key pillars in the treatment of chronic obstructive diseases, such as asthma and COPD (Chronic obstructive pulmonary disease); however, wide number of errors occur with high frequency in the inhalation manoeuvres among these patient. This review discuss the main errors made with inhalation devices, factors associated with poor IT (inhalation technique), their consequences and possible solutions. DATA SOURCES: To do this, we performed a search of any publications available in PubMed between the years 2000 and 2019, using the key words: asthma, COPD, obstructive lung disease, inhalers, misuse and errors. STUDY SELECTIONS: After a review of the titles and abstracts by the working group, the articles chosen were considered the most relevant in providing evidence of the problems and establishing solutions in the inhalation treatment of asthma and COPD. RESULTS: There are several publications that associated the errors in the inhalation technique with a poor prognosis both of asthma and COPD. Most authors generally agree in that a poor IT is associated with poor control of the symptoms. CONCLUSIONS: It is essential to review the IT in all our patients with asthma and COPD due to the high socio-economic impact that it involves; an effort must be made to homogenise the evaluation of IT, so that it helps to transmit a clear message to the patients, as well as to the health professionals on what is and what is not a correct manoeuvre.

Impact of Hyponatremia on COPD Exacerbation Prognosis.

The most common electrolyte disorder among hospitalized patients, hyponatremia is a predictor of poor prognosis in various diseases. The aim of this study was to establish the prevalence of hyponatremia in patients admitted for acute exacerbation of chronic obstructive pulmonary disease (AECOPD), as well as its association with poor clinical progress. Prospective observational study carried out from 1 October 2016 to 1 October 2018 in the following hospitals: Salnés in Vilagarcía de Arousa, Arquitecto Marcide in Ferrol, and the University Hospital Complex of Santiago de Compostela, Galicia, Spain, on patients admitted for AECOPD. Patient baseline treatment was identified, including hyponatremia-inducing drugs. Poor progress was defined as follows: prolonged stay, death during hospitalization, or readmission within one month after the index episode discharge. 602 patients were enrolled, 65 cases of hyponatremia (10.8%) were recorded, all of a mild nature (mean 131.6; SD 2.67). Of all the patients, 362 (60%) showed poor progress: 18 (3%) died at admission; 327 (54.3%) had a prolonged stay; and 91 (15.1%) were readmitted within one month after discharge. Patients with hyponatremia had a more frequent history of atrial fibrillation (AF) (p 0.005), pleural effusion (p 0.01), and prolonged stay (p 0.01). The factors independently associated with poor progress were hyponatremia, pneumonia, and not receiving home O2 treatment prior to admission. Hyponatremia is relatively frequent in patients admitted for AECOPD, and it has important prognostic implications, even when mild in nature.

Obesity Does Not Increase the Risk of Asthma Readmissions.

The relationship between obesity and asthma exacerbations is still under debate. The aim of our work is to analyse the relationship between obesity and hospital re-admissions in asthmatics. A review was retrospectively performed on all hospital admissions of adult patients due to asthma exacerbation occurring in our hospital for 11 years. All those cases with asthma as the first diagnosis in the discharge report were included, or those with asthma as the second diagnosis provided when the first diagnosis was respiratory infection or respiratory failure. Only the first hospital admission of each patient was included in this study. The Odds Ratios of a higher incidence of early/late readmissions due to asthma exacerbation were calculated using a binary logistic regression, using the body mass index (BMI) as independent variable, adjusted for all the variables included in the study. The study included 809 patients with a mean age of 55.6 years, and 65.2% were female. The majority (71.4%) were obese or overweight. No significant relationship was observed in the univariate or multivariate analyses between overweight or obesity and the early or late hospital readmissions due to asthma. Therefore, obesity does not seem to be a determining factor in the risk of asthma exacerbations.

Characteristics of patients with pseudochylothorax-a systematic review.

BACKGROUND: Pseudochylothorax (PCT) (cholesterol pleurisy or chyliform effusion) is a cholesterol-rich pleural effusion (PE) that is commonly associated with chronic inflammatory disorders. Nevertheless, the characteristics of patients with PCT are poorly defined. METHODS: A systematic review was performed across two electronic databases searching for studies reporting clinical findings, PE characteristics, and the most effective treatment of PCT. Case descriptions and retrospective studies were included. RESULTS: The review consisted of 62 studies with a total of 104 patients. Median age was 58 years, the male/female ratio was 2.6/1, and in the 88.5% of cases the etiology was tuberculosis (TB) or rheumatoid arthritis (RA). PE was usually unilateral (88%) and occupied greater than one-third of the hemithorax (96.3%). There was no evidence of pleural thickening in 20.6% of patients, and 14 patients had a previous PE. The pleural fluid (PF) was an exudate, usually milky (94%) and with a predominance of lymphocytes (61.1%). The most sensitive tests to establish the diagnosis were the cholesterol/triglycerides ratio (CHOL/TG ratio) >1, and the presence of cholesterol crystals (97.4% and 89.7%, respectively). PF culture for TB was positive in the 34.1% of patients. Favorable outcomes with medical treatment, therapeutic thoracentesis, decortication/pleurectomy, pleurodesis, thoracic drainage and thoracoscopic drainage were achieved in 78.9%, 47.8%, 86.7%, 66.6%, 37.5% and 42.9%, respectively. CONCLUSIONS: PCT is usually tuberculous or rheumatoid, unilateral and the PF is a milky exudate. The presence of cholesterol crystals and a CHOL/TG ratio >1 are the most sensitive test for the diagnosis. The lack of pleural thickening does not rule out PCT. Treatment should be sequential, treating the underlying causes, and assessing the need for interventional techniques.