Bronchodilator Response in Post-COVID-19 Patients Undergoing Pulmonary Rehabilitation.

INTRODUCTION: SARS-CoV-2 infections can result in a broad spectrum of symptoms from mild to life-threatening. Long-term consequences on lung function are not well understood yet. METHODS: In our study, we have examined 134 post-COVID patients (aged 54.83 ± 14.4 years) with dyspnea on exertion as a leading symptom 6 weeks to 24 months after a SARS-CoV-2 infection for bronchodilator responsiveness during their stay in our pulmonary rehabilitation clinic. RESULTS: Prior to bronchial dilation, 6 out of 134 patients (4.47%) presented an FEV1/FVC ratio below lower limit of normal (Z-score = -1.645) indicative of an obstructive airway disease. Following inhalation of a ß2-adrenergic agonist we measured a mean FEV1 increase of 181.5 mL in our cohort, which was significantly elevated compared to a historical control group (ΔFEV1 = 118 mL). 28.7% of the patients showed an increase greater than 200 mL and 12% displayed a significant bronchodilation response (>200 mL ΔFEV1 and >12% FEV1 increase). Interestingly, no significant difference in bronchial dilation effect was observed when comparing patients hospitalized and those non-hospitalized during the course of their SARS-CoV-2 infection. CONCLUSION: Our data provide evidence for increased prevalence of obstructive ventilatory defects and increased bronchodilator responsiveness in patients with persisting symptoms after COVID-19. Depending on the extent of this complication, post-COVID patients may benefit from an adapted ß2-inhalation therapy including subsequent reevaluation.

[Diagnosis and treatment of asthma: a guideline for respiratory specialists 2023 - published by the German Respiratory Society (DGP) e. V.] / S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023.

The management of asthma has fundamentally changed during the past decades. The present guideline for the diagnosis and treatment of asthma was developed for respiratory specialists who need detailed and evidence-based information on the new diagnostic and therapeutic options in asthma. The guideline shows the new role of biomarkers, especially blood eosinophils and fractional exhaled NO (FeNO), in diagnostic algorithms of asthma. Of note, this guideline is the first worldwide to announce symptom prevention and asthma remission as the ultimate goals of asthma treatment, which can be achieved by using individually tailored, disease-modifying anti-asthmatic drugs such as inhaled steroids, allergen immunotherapy or biologics. In addition, the central role of the treatment of comorbidities is emphasized. Finally, the document addresses several challenges in asthma management, including asthma treatment during pregnancy, treatment of severe asthma or the diagnosis and treatment of work-related asthma.

[Chronic obstructive pulmonary disease, sleep-disordered breathing and hypoventilation-Influence on the cardiorenal system]. / Chronisch-obstruktive Lungenerkrankung, schlafbezogene Atemstörungen und Hypoventilation ­ Einflüsse auf das kardiorenale System.

Comorbidities are frequently observed in patients suffering from pulmonary diseases due to shared risk factors and intricate interactions between various organ systems. This article aims to characterize the effects of selected diseases of the respiratory system on the cardiovascular system and kidneys. Advanced chronic obstructive pulmonary disease (COPD) often leads to a prognostically unfavorable increased pressure in the pulmonary circulation. In this respect treatment of these patients is primarily aimed at the underlying pulmonary disease and targeted treatment of the pulmonary hypertension should only be carried out according to invasive diagnostics and in an individualized manner. So far, the fact that there is a substantial overlap between COPD and heart failure with preserved ejection fraction has been completely ignored, which should be considered in the diagnostic procedure. Obstructive sleep apnea (OSA) has several unfavorable effects on the cardiovascular system and has been identified as an independent risk factor for cardiovascular diseases. The established treatment of OSA with continuous positive airway pressure (CPAP) has been shown to improve daytime sleepiness and the quality of life; however, an effect of CPAP on the occurrence of cardiovascular events, especially in asymptomatic patients, has so far not been demonstrated in randomized trials. Peripheral edema is frequently observed in patients suffering from chronic hypercapnia, which can be explained by several pathophysiological mechanisms, including pulmonary vasoconstriction and a direct effect of the hypercapnia on renal blood flow. Apart from the administration of diuretics, recompensation of such patients always requires treatment of the hypercapnia by noninvasive ventilation.

The Distribution of Alpha-1 Antitrypsin Genotypes Between Patients with COPD/Emphysema, Asthma and Bronchiectasis.

Purpose: Alpha-1-antitrypsin deficiency (AATD) is a rare hereditary condition characterized by low circulating levels of alpha-1antitrypsin (AAT). While the association between AATD and COPD/emphysema is undisputed, the association between AATD and asthma or bronchiectasis is still a matter of debate. Aims and Objectives: Our study aimed to investigate the distribution of AAT genotypes between patients with COPD/emphysema, asthma and bronchiectasis. To back up the diagnostic labels, we described symptoms associated with the diagnosis. Methods: Between September 2003 and March 2020, 29,465 testing kits (AlphaKit®) were analyzed in the AAT laboratory, University of Marburg, Germany. The diagnosis of AATD has been made based on the measurements of AAT serum levels, followed by genotyping, phenotyping or whole gene sequencing depending on the availability and/or the need for more detailed interpretation of the results. The respiratory symptoms were recorded as well. Results: Regarding the distribution of the wild type allele M and the most frequent mutations S (E264V) and Z (E342K), no significant differences could be found between COPD/emphysema [Pi*MM (58.24%); Pi*SZ (2.49%); Pi*ZZ (9.12%)] and bronchiectasis [Pi*MM (59.30%) Pi*SZ (2.81%); Pi*ZZ (7.02%)]. When COPD/emphysema and bronchiectasis were recorded in the same patient, the rate of Pi* ZZ (14.78%) mutations was even higher. Asthma patients exhibited significantly less deficient genotypes [Pi*MM (54.81%); Pi*SZ (2%); Pi*ZZ (2.77%)] than two other groups. Associated respiratory symptoms confirmed the diagnosis. Conclusion: COPD/emphysema and bronchiectasis, but not asthma patients, exhibit higher frequency of AATD genotypes. Our data suggest that AATD testing should be offered to patients with COPD/emphysema and bronchiectasis.

Diagnosing Alpha-1-Antitrypsin Deficiency Using A PCR/Luminescence-Based Technology.

Purpose: Alpha-1-antitrypsin deficiency (AATD) is a rare hereditary condition resulting from the mutations in the SERPINA1 (serine protease inhibitor) gene and is characterized by low circulating levels of the alpha-1 antitrypsin (AAT) protein. The traditional algorithm for laboratory testing of AATD involves the analysis of AAT concentrations (nephelometry), phenotyping (isoelectric focusing, IEF), and genotyping (polymerase chain reaction, PCR); in selected cases, full sequencing of the SERPINA1 gene can be undertaken. New technologies arise that may make diagnosis easier and faster. Methods: We developed and evaluated a new diagnostic algorithm based on Luminex xMAP (multi-analyte profiling) technology using Progenika A1AT Genotyping Test. In an initial learning phase, 1979 samples from individuals suspected of having AATD were examined by both, a traditional and a "new" algorithm. In a second phase, 1133 samples were analyzed with the Luminex xMAP only. Results: By introducing a Luminex xMAP based algorithm, we were able to simultaneously identify 14 mutations in SERPINA1 gene (instead of two- S and Z-by using our old algorithm). Although the quantity of IEF assays remained unchanged, the nephelometric measurements and sequencing were reduced by 79% and 63.4%, respectively. Conclusion: The new method is convenient, fast and user-friendly. The application of the Luminex xMAP technology can simplify and shorten the diagnostic workup of patients with suspected AATD.

Anti-interleukin-5 therapy (mepolizumab) in life-threatening asthma attack: A case-based discussion.

We report about a case of a compassionate off-label use of the anti-interleukin-5-agent mepolizumab in a ventilated patient with life-threatening asthma attack in eosinophilic asthma. The patient suffered from severe eosinophilic asthma and was transmitted to our hospital with an asthma attack and a life-threatening respiratory state under ventilation. Since high dose steroids had not yielded a sufficient respiratory improvement mepolizumab was administered subcutaneously. After administration of mepolizumab respiratory state and ventilation parameter improved significantly. Two days after administration the patient was weaned could be extubated 8 days later and recovered completely from the asthma attack. The presented clinical case is suggestive of future clinical trials or registry studies to evaluate potential clinical benefits of anti-interleukin-5 treatment in patients with severe exacerbations of eosinophilic asthma.

[Screening and check-ups in pneumology]. / Vorsorgeuntersuchungen und Check-ups in der Pneumologie.

In pneumology, preventive check-ups have played a subordinate role so far. Current research results could change this. In the following article the focus is on lung cancer and COPD, diseases that have a considerable influence on mortality and morbidity in modern society. Approaches will be discussed that will allow earlier diagnosis of COPD or identify patients at risk. In particular Capture, a questionnaire that significantly increases the pre-test probability in COPD diagnostics, should be mentioned here. Lung carcinoma screening is a controversial topic in Germany. In an American study, the relative mortality rate from lung cancer was significantly reduced by CT screening. Results of a European study (Nelson trial) are still pending. A high pre-test probability will also be decisive for lung cancer screening. In this way, the cost-benefit ratio could be optimized. Since COPD patients have a significantly increased risk of lung cancer, there might be overlaps in the screening procedures.

COPD as a risk factor of the complications in lower limb arthroplasty: a patient-matched study.

Purpose: A relevant proportion of patients undergoing joint replacement surgery for the treatment of osteoarthritis exhibit COPD. This coincidence may result from an increased prevalence of both the diseases in elderly patients. In this study, COPD, which is known to be associated with a variety of comorbidities, and its potential interactions, eg, mediated via systemic inflammation, are discussed. The purpose of the present study was to identify the role of COPD as an independent risk factor for complications after total knee and hip arthroplasty. Patients and methods: In a monocentric patient cohort of 2,760 arthoplasties, propensity score matching was done using the following factors: sex, age, replaced joint, American Society of Anesthesiologists' score, body mass index, hypertension, chronic heart disease, anticoagulation, diabetes mellitus, chronic renal deficiency, and actual smoking status to create 224 pairs. Both the pre-matched differences and the results after propensity score matching were statistically analyzed with p≤0.05 being defined as statistically significant. Results: All confounders were eliminated after matching. Preoperatively measured C-reactive protein and leukocytes were higher in the COPD group (p<0.001; p=0.01, respectively). Intensive care unit admission was higher for COPD patients (p=0.023). Pneumonia occurred in patients with COPD only (p=0.024). There was a trend (not significant) toward a higher rate of wound infections, increased transfusion of red blood cells, and a prolonged hospital stay in patients with COPD. Conclusion: COPD was associated with an increased length of hospital stay, a higher risk of pneumonia and wound infection, higher general complications, and an increased need for red blood cell transfusion. It is thus recommended to enhance the implementation of pneumonia prevention programs on surgical wards.

The prevalence of diagnosed α1-antitrypsin deficiency and its comorbidities: results from a large population-based database.

α1-Antitrypsin deficiency (AATD) is a genetically determined disorder that is associated with different clinical manifestations. We aimed to assess the prevalence of diagnosed AATD and its comorbidities using a large healthcare database.In this retrospective longitudinal observational study, we analysed data from 4 million insurants. Using International Classification of Diseases revision 10 (ICD-10) codes, we assessed the prevalence, comorbidities and healthcare utilisation of AATD patients (E88.0 repeatedly coded) relative to non-AATD patients with chronic obstructive pulmonary disease (COPD), emphysema or asthma.In our study population, we identified 673 AATD patients (590 aged ≥30 years), corresponding to a prevalence of 23.73 per 100 000 in all age groups and 29.36 per 100 000 in those ≥30 years. Based on the number of AATD cases detected in the sample size (673 out of 2 836 585), we extrapolated that there were 19 162 AATD cases in Germany during the years studied. AATD patients had a higher prevalence of arterial hypertension, chronic kidney disease and diabetes relative to non-AATD asthma or emphysema patients. When compared to non-AATD COPD patients, AATD patients had significantly more consultations and more frequent and longer hospitalisations.Our data strengthen the assumption that AATD is associated with a variety of other diseases. Healthcare utilisation appears to be higher among AATD patients as compared to patients with non-AATD-related obstructive lung diseases.

Therapy with plasma purified alpha1-antitrypsin (Prolastin®) induces time-dependent changes in plasma levels of MMP-9 and MPO.

The common Z mutation (Glu342Lys) of α1-antitrypsin (A1AT) results in the polymerization and intracellular retention of A1AT protein. The concomitant deficiency of functional A1AT predisposes PiZZ subjects to early onset emphysema. Clinical studies have implied that, among the biomarkers associated with emphysema, matrix metalloproteinase 9 (MMP-9) is of particular importance. Increased plasma MMP-9 levels are proposed to predict the decline of lung function as well as greater COPD exacerbations in A1AT deficiency-associated emphysema. The aim of the present study was to investigate the effect of A1AT therapy (Prolastin) on plasma MMP-9 and myeloperoxidase (MPO) levels. In total 34 PiZZ emphysema patients were recruited: 12 patients without and 22 with weekly intravenous (60 mg/kg body weight) A1AT therapy. The quantitative analysis of A1AT, MMP-9 and MPO was performed in serum and in supernatants of blood neutrophils isolated from patients before and after therapy. Patients with Prolastin therapy showed significantly lower serum MMP-9 and MPO levels than those without therapy. However, parallel analysis revealed that a rapid infusion of Prolastin is accompanied by a transient elevation of plasma MMP-9 and MPO levels. Experiments with freshly isolated blood neutrophils confirmed that therapy with Prolastin causes transient MMP-9 and MPO release. Prolastin induced the rapid release of MMP-9 and MPO when added directly to neutrophil cultures and this reaction was associated with the presence of IgA in A1AT preparation. Our data support the conclusion that changes in plasma levels of MMP-9 and MPO mirror the effect of Prolastin on blood neutrophils.

Detection of obstructive sleep apnoea by an electronic nose.

Diagnosis of obstructive sleep apnoea syndrome (OSAS) is technically demanding, cost-intensive and time-consuming. The measurement of volatile organic compounds by an electronic nose is an innovative method that determines distinct molecular patterns of exhaled breath in different patient groups. We addressed the following questions: What is the diagnostic accuracy of an electronic nose in the detection of OSAS and the ability to detect effects of standard therapy in patients with OSAS? Are these results related to changes in distinct markers of airway inflammation and extracellular remodelling? We included 40 OSAS patients and 20 healthy controls. Exhaled breath of all participants was analysed using the Cyranose 320 electronic nose. Pharyngeal washings were performed to sample the upper airway compartment. For statistical analysis linear discriminant analysis was employed. We identified a linear discriminant function separating OSAS from control (p<0.0001). The corresponding area under the receiver-operating curve was 0.85 (95% CI 0.75-0.96; sensitivity 0.93 and specificity 0.7). In pharyngeal washing fluids of OSAS patients, we observed higher levels of α1-antitrypsin and markers of extracellular remodelling compared to controls. The electronic nose can distinguish between OSAS patients and controls with high accuracy.