PURPOSE: Chronic pulmonary conditions require complex treatment strategies involving long-term antibiotic treatment, which carries the highest risk of antimicrobial resistance and adverse drug events (ADE). Specific guidance on prescribing and deprescribing can help reduce these risks and improve therapy effectiveness. The aim of the study was to determine prescribing and deprescribing practices for long-term antibiotic treatment (≥30 days) in preventing exacerbations of stable chronic pulmonary conditions in adult patients across all healthcare settings. PATIENTS AND METHODS: This umbrella review was part of a larger registered study (PROSPERO, CRD42022381268) including systematic reviews and meta-analyses retrieved from PubMed, Cochrane Library, and PsycInfo. Outcomes of interest included condition, antibiotic, dose, duration, (de-) prescribing advice. Standardized methodological tools were used to assess methodological quality of the selected publications (ROBIS), facilitate data extraction (EPOC), and guide narrative summary of findings (PRIOR). RESULTS: In total, n = 14 publications were analyzed. (De-)prescribing advice is summarized for treatment (≥30 days) of chronic obstructive pulmonary disease, asthma, non-cystic fibrosis bronchiectasis, cystic fibrosis, and bronchiolitis obliterans syndrome. Macrolides are the most commonly recommended antibiotic for stable chronic pulmonary conditions. ADEs are the main reason for antibiotic discontinuation. Little consideration is given to emergence of antibiotic resistance. CONCLUSION: There is a significant paucity of literature providing specific (de-)prescribing advice for clinical practice. More precise recommendations are required in view of patient safety.

• Keywords
• Chronic obstructive pulmonary disease, antibiotics, asthma, bronchiolitis obliterans syndrome, lung diseases, non-cystic fibrosis bronchiectasis,
• MeSH
• Anti-Bacterial Agents * therapeutic use   MeSH
• Asthma drug therapy   MeSH
• Bronchiectasis drug therapy   MeSH
• Chronic Disease MeSH
• Pulmonary Disease, Chronic Obstructive drug therapy   MeSH
• Cystic Fibrosis drug therapy   MeSH
• Deprescriptions * MeSH
• Practice Patterns, Physicians' * MeSH
• Humans MeSH
• Meta-Analysis as Topic MeSH
• Lung Diseases * drug therapy   MeSH
• Systematic Reviews as Topic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Systematic Review MeSH
• Names of Substances
• Anti-Bacterial Agents * MeSH

BACKGROUND: Sex and gender influence many aspects of chronic obstructive pulmonary disease (COPD). Limited data are available on this topic in alpha-1 antitrypsin deficiency (AATD). We therefore aimed to investigate sex issues in the EARCO registry, a prospective, international, observational cohort study. METHODS: Baseline data from PiZZ individuals, enrolled in the registry with complete data on sex and smoking history were analysed by group comparisons and binary logistic regression analyses. RESULTS: 1283 patients with AATD, 49.3% women were analysed. Females reported less tobacco consumption (16.8±12.2 vs. 19.6±14.5 PY, p=0.006), occupational exposures towards gases, dusts or asbestos (p<0.005 each) and consumed less alcohol (5.5±7.6 vs. 8.4±10.3u/week, p<0.001). Females reported COPD (41% vs. 57%, p<0.001) and liver disease (11% vs. 20%, p<0.001) less often. However, they had a higher prevalence of bronchiectasis (24% vs. 13%, p<0.001). Despite better lung function (FEV1%pred. 73.6±29.9 vs. 62.7±29.5, p<0.001) females reported a similar symptom burden (CAT 13.4±9.5 vs. 12.5±8.9, p=ns) and exacerbation frequency (at least one in the previous year 30% vs. 26%, p=ns) compared to males. In multivariate analyses, female sex was an independent risk factor for exacerbations in the previous year OR 1.6 p=0.001 in addition to smoking history, COPD, asthma and bronchiectasis and was also identified as risk factors for symptom burden (CAT≥10) OR 1.4 p=0.014 besides age, BMI, COPD and smoking history. CONCLUSION: Men had higher rates of COPD and liver disease, women were more likely to have bronchiectasis. Women's higher symptom burden and exacerbation frequency suggest they may need tailored treatment approaches.

• Keywords
• Alpha1-antitrypsin, Alpha1-antitrypsin deficiency, Chronic obstructive pulmonary disease, Gender,
• MeSH
• Bronchiectasis epidemiology   etiology   MeSH
• Pulmonary Disease, Chronic Obstructive epidemiology   etiology   MeSH
• alpha 1-Antitrypsin Deficiency * epidemiology   complications   MeSH
• Comorbidity MeSH
• Smoking epidemiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Liver Diseases epidemiology   etiology   MeSH
• Alcohol Drinking epidemiology   MeSH
• Occupational Exposure adverse effects   MeSH
• Prevalence MeSH
• Prospective Studies MeSH
• Registries * MeSH
• Aged MeSH
• Sex Factors MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH
• Comparative Study MeSH

BACKGROUND: Primary ciliary dyskinesia (PCD) represents a group of rare hereditary disorders characterised by deficient ciliary airway clearance that can be associated with laterality defects. We aimed to describe the underlying gene defects, geographical differences in genotypes and their relationship to diagnostic findings and clinical phenotypes. METHODS: Genetic variants and clinical findings (age, sex, body mass index, laterality defects, forced expiratory volume in 1 s (FEV1)) were collected from 19 countries using the European Reference Network's ERN-LUNG international PCD Registry. Genetic data were evaluated according to American College of Medical Genetics and Genomics guidelines. We assessed regional distribution of implicated genes and genetic variants as well as genotype correlations with laterality defects and FEV1. RESULTS: The study included 1236 individuals carrying 908 distinct pathogenic DNA variants in 46 PCD genes. We found considerable variation in the distribution of PCD genotypes across countries due to the presence of distinct founder variants. The prevalence of PCD genotypes associated with pathognomonic ultrastructural defects (mean 72%, range 47-100%) and laterality defects (mean 42%, range 28-69%) varied widely among countries. The prevalence of laterality defects was significantly lower in PCD individuals without pathognomonic ciliary ultrastructure defects (18%). The PCD cohort had a reduced median FEV1 z-score (-1.66). Median FEV1 z-scores were significantly lower in CCNO (-3.26), CCDC39 (-2.49) and CCDC40 (-2.96) variant groups, while the FEV1 z-score reductions were significantly milder in DNAH11 (-0.83) and ODAD1 (-0.85) variant groups compared to the whole PCD cohort. CONCLUSION: This unprecedented multinational dataset of DNA variants and information on their distribution across countries facilitates interpretation of the genetic epidemiology of PCD and indicates that the genetic variant can predict diagnostic and phenotypic features such as the course of lung function.

• MeSH
• Axonemal Dyneins genetics   MeSH
• Cytoskeletal Proteins MeSH
• Child MeSH
• Adult MeSH
• Phenotype * MeSH
• Genetic Variation MeSH
• Genetic Association Studies * MeSH
• Genotype * MeSH
• Kartagener Syndrome genetics   physiopathology   MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Mutation MeSH
• Child, Preschool MeSH
• Proteins MeSH
• Registries MeSH
• Aged MeSH
• Forced Expiratory Volume MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH
• Names of Substances
• Axonemal Dyneins MeSH
• CCDC39 protein, human MeSH Browser
• CCDC40 protein, human MeSH Browser
• Cytoskeletal Proteins MeSH
• DNAH11 protein, human MeSH Browser
• Proteins MeSH

• Keywords
• infant, infant lung function, primary ciliary dyskinesia, ventilation inhomogeneity,
• MeSH
• Cilia MeSH
• Kartagener Syndrome * complications   MeSH
• Infant MeSH
• Humans MeSH
• Lung MeSH
• Ciliary Motility Disorders * complications   MeSH
• Check Tag
• Infant MeSH
• Humans MeSH
• Publication type
• Letter MeSH
• Geographicals
• Czech Republic epidemiology   MeSH

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).

• Keywords
• Alpha-1 antitrypsin, Phenotypes, Registry,
• MeSH
• alpha 1-Antitrypsin genetics   MeSH
• Bronchiectasis * diagnosis   epidemiology   MeSH
• Pulmonary Disease, Chronic Obstructive * genetics   MeSH
• alpha 1-Antitrypsin Deficiency * diagnosis   epidemiology   genetics   MeSH
• Genotype MeSH
• Humans MeSH
• Pulmonary Emphysema * diagnosis   epidemiology   complications   MeSH
• Prospective Studies MeSH
• Cross-Sectional Studies MeSH
• Registries MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Names of Substances
• alpha 1-Antitrypsin MeSH

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease.

• Keywords
• CVID, Chest CT, bronchial pathology, bronchiectasis, primary antibody deficiency,
• MeSH
• Common Variable Immunodeficiency pathology   MeSH
• Bronchiectasis pathology   MeSH
• Bronchi pathology   MeSH
• Child MeSH
• Adult MeSH
• Thoracic Wall pathology   MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Tomography, X-Ray Computed methods   MeSH
• Child, Preschool MeSH
• Aged MeSH
• Spirometry methods   MeSH
• Immunologic Deficiency Syndromes pathology   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH

Bronchiectasis is a clinically important, but poorly understood, pulmonary condition characterized by dilated and thick-walled bronchi. Bronchiectasis remains a significant cause of morbidity and mortality around the world. Targeted effort to early high-resolution computed tomography diagnosis and detailed confirmation of causation are in the spotlight of respiratory physicians in the developed countries. The risk population consists of subjects with persistent and/or productive cough, where another clear diagnosis has not been performed. Specific treatment tailored on underlying diseases and non-specific airway clearance techniques are able to improve symptoms, and reduce lung impairment. Evidence-based treatment algorithms for anti-inflammatory, and antibiotic treatment of stable non-CF BE will have to await large-scale, long-term controlled studies. Surgery should be reserved for individuals with highly symptomatic, localized bronchiectasis who have failed medical management. Unfortunately, there have been few well designed longitudinal or cross-sectional studies in the field of bronchiectasis. To give truly meaningful and generalizable results, a longitudinal observational study of bronchiectasis would require to enrol several thousand patients, more than any one center can enrol. The European Bronchiectasis Registry will create an open, pan-European registry of patients with non-CF bronchiectasis. The authors emphatically recommend that all respiratory specialist managed non-CF BE subjects should be actively involved in the European Bronchiectasis Registry.Key words: bronchiectasis - diagnosis - registry - treatment.

• MeSH
• Bronchiectasis * MeSH
• Humans MeSH
• Cross-Sectional Studies MeSH
• Registries MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Geographicals
• Czech Republic MeSH

The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no "gold standard" reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia.

• MeSH
• Cilia pathology   ultrastructure   MeSH
• Delphi Technique MeSH
• Diagnosis, Differential MeSH
• Fluorescent Antibody Technique MeSH
• Genetic Testing MeSH
• Kartagener Syndrome diagnosis   genetics   MeSH
• Humans MeSH
• Nitric Oxide analysis   MeSH
• Review Literature as Topic MeSH
• Societies, Medical MeSH
• Microscopy, Electron, Transmission MeSH
• Microscopy, Video MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Practice Guideline MeSH
• Geographicals
• Europe MeSH
• Names of Substances
• Nitric Oxide MeSH

INTRODUCTION: There is an increasing number of cystic fibrosis (CF) patients with the diagnosis established in adulthood worldwide. AIM: To give an overview of our experience with the diagnostics of CF in adulthood in the Czech Republic. METHODS: CF patients with the diagnosis determined at the age 18 years during 2000-2014 period were selected from the Czech Registry of CF (www.cfregistr.cz). Demographic and clinical data were reported from medi-cal records at the time of diagnosis and as of 31st December 2014. Only those with two CF causing mutation or with one CF causing mutation together with sweat chloride concentration > 60 mmol/l were included in the study. The clinical presentation was compared with a control group consisting of homozygous F508del patients with the diagnosis established in childhood. RESULTS: 23 patients (16 men and 7 women) with the diagnosis determined at a mean age of 32.9 ± 8.5 years were included in the study. Presenting symptoms included bronchiectasis and/or haemoptysis in 12 cases, obstructive azoospermia in 7 cases and recurrent pancreatitis in 4 cases. When compared with the control group, the patients had higher age (38.6 ± 8.3 vs. 28.3 ± 4.7 years; p < 0.001), a lower concentration of sweat chloride (62 ± 23 vs. 90 ± 12 mmol/l; p < 0.001), less frequent airway infections with Pseudomonas aeruginosa and/or Burkholderia cepacia complex (4 vs. 12; p = 0.029), bronchiectasis (14 vs. 23; p = 0.001), exocrine pancreatic insufficiency (1 vs. 23; p < 0.001) and therapy with insulin (1 vs. 9; p = 0.01); on the contrary, pancreatitis was more frequent (6 vs. 0; p = 0.022). CONCLUSION: Diagnosis of CF in adults should be considered in those with corresponding symptoms in respiratory, digestive and reproductive tract. Clinical presentation differs from classical CF in many parameters. KEY WORDS: adults - cystic fibrosis - diagnostics.

• MeSH
• Azoospermia etiology   MeSH
• Bronchiectasis etiology   MeSH
• Pancreatitis, Chronic etiology   MeSH
• Cystic Fibrosis complications   diagnosis   genetics   MeSH
• Adult MeSH
• Exocrine Pancreatic Insufficiency etiology   MeSH
• Hemoptysis etiology   MeSH
• Humans MeSH
• Mutation MeSH
• Registries MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

BACKGROUND: Increased expression of the human epididymis protein 4 (HE4) was previously described in lung biopsy samples from patients with cystic fibrosis (CF). It remains unknown, however, whether serum HE4 concentrations are elevated in CF. METHODS: Seventy-seven children with CF from six Hungarian CF centers and 57 adult patients with CF from a Czech center were enrolled. In addition, 94 individuals with non-CF lung diseases and 117 normal control subjects with no pulmonary disorders were analyzed. Serum HE4 levels were measured by using an immunoassay, and their expression was further investigated via the quantification of HE4 messenger RNA by using quantitative reverse transcription polymerase chain reaction in CF vs non-CF respiratory epithelium biopsy specimens. The expression of the potential regulator miR-140-5p was analyzed by using an UPL-based quantitative reverse transcription polymerase chain reaction assay. HE4 was measured in the supernatants from unpolarized and polarized cystic fibrosis bronchial epithelial cells expressing wild-type or F508del-CFTR. RESULTS: Median serum HE4 levels were significantly elevated in children with CF (99.5 [73.1-128.9] pmol/L) compared with control subjects (36.3 [31.1-43.4] pmol/L; P < .0001). This observation was replicated in adults with CF (115.7 [77.8-148.7] pmol/L; P < .0001). In contrast, abnormal but lower HE4 concentrations were found in cases of severe bronchitis, asthma, pneumonia, and bronchiectasis. In patients with CF, the concentrations of HE4 were positively correlated with overall disease severity and C-reactive protein concentrations, whereas a significant inverse relationship was found between HE4 and the spirometric FEV1 value. Relative HE4 mRNA levels were significantly upregulated (P = .011) with a decreased miR-140-5p expression (P = .020) in the CF vs non-CF airway biopsy specimens. Twofold higher HE4 concentrations were recorded in the supernatant of polarized F508del-CF transmembrane conductance regulator/bronchial epithelial cells compared with wild-type cells. CONCLUSIONS: HE4 serum levels positively correlate with the overall severity of CF and the degree of pulmonary dysfunction. HE4 may thus be used as a novel inflammatory biomarker and possibly also as a measure of treatment efficacy in CF lung disease.

• Keywords
• CFTR mutations, CRP, FEV(1), HE4, cystic fibrosis, inflammation, sweat test,
• MeSH
• Asthma genetics   metabolism   MeSH
• Bronchiectasis genetics   metabolism   MeSH
• Bronchitis genetics   metabolism   MeSH
• C-Reactive Protein metabolism   MeSH
• Cystic Fibrosis genetics   metabolism   physiopathology   MeSH
• Child MeSH
• Adult MeSH
• Epithelial Cells metabolism   MeSH
• Humans MeSH
• RNA, Messenger metabolism   MeSH
• MicroRNAs metabolism   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Pneumonia genetics   metabolism   MeSH
• Reverse Transcriptase Polymerase Chain Reaction MeSH
• Child, Preschool MeSH
• Cystic Fibrosis Transmembrane Conductance Regulator genetics   MeSH
• WAP Four-Disulfide Core Domain Protein 2 MeSH
• Proteins genetics   metabolism   MeSH
• Respiratory Mucosa metabolism   MeSH
• Spirometry MeSH
• Case-Control Studies MeSH
• Severity of Illness Index MeSH
• Forced Expiratory Volume MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• C-Reactive Protein MeSH
• CFTR protein, human MeSH Browser
• RNA, Messenger MeSH
• MicroRNAs MeSH
• Mirn140 microRNA, human MeSH Browser
• Cystic Fibrosis Transmembrane Conductance Regulator MeSH
• WAP Four-Disulfide Core Domain Protein 2 MeSH
• Proteins MeSH
• WFDC2 protein, human MeSH Browser