UNASSIGNED: The study aimed to compare prevalence of comorbid allergic manifestations and rhinitis, allergy testing and associations with patient-related outcomes in patients with asthma and COPD.
UNASSIGNED: Cross-sectional study of randomly selected Swedish patients with a doctor\'s diagnosis of asthma (n = 1291) or COPD (n = 1329). Self-completion questionnaires from 2014 provided data on demographics, rhinitis, allergic symptoms at exposure to pollen or furry pets, exacerbations, self-assessed severity of disease and scores from the Asthma Control Test (ACT) and the COPD Assessment Test (CAT), and records were reviewed for allergy tests.
UNASSIGNED: Allergic manifestations were more common in asthma (75%) compared with COPD (38%). Rhinitis was reported in 70% of asthma and 58% of COPD patients. Allergy tests had been performed during the previous decade in 28% of patients with asthma and in 8% of patients with COPD.In patients with asthma; comorbid allergy and rhinitis were both independently associated with increased risk for poor asthma symptom control (ACT < 20) (OR [95% CI] 1.41 [1.05 to 1.87] and 2.13 [1.60 to 2.83]), exacerbations (1.58 [1.15 to 2.17] and 1.38 [1.02 to 1.86]), and self-assessed moderate/severe disease (1.64 [1.22 to 2.18] and 1.75 [1.33 to 2.30]). In patients with COPD, comorbid allergy and rhinitis were both independently associated with increased risk for low health status (CAT ≥ 10) (OR [95% CI] 1.46 [1.20 to 1.95] and 2.59 [1.97 to 3.41]) respectively, with exacerbations during the previous six months (1.91 [1.49 to 2.45] and 1.57 [1.23 to 2.01]), and with self-assessed moderate/severe disease (1.70 [1.31 to 2.22] and 2.13 [1.66 to 2.74]).
UNASSIGNED: Allergic manifestations and rhinitis are more common in asthma than COPD but associated with worse outcomes in both diseases. This highlights the importance of examining and treating comorbid allergy and rhinitis, not only in asthma but also in COPD.

Background: Bronchiectasis (BE) has been traditionally associated with neutrophilic inflammation, but eosinophilic bronchiectasis (EB) has recently emerged. Data about prevalence, clinical features, and disease severity are lacking. This study aimed to assess the EB prevalence, compare EB with non-EB, evaluate the Type-2 (T2) high endotype in BE (T2-high EB) versus non-T2-high EB, and identify EB predictors. Methods: We conducted a prospective study involving 153 BE patients. The data collected included clinical, radiological, and microbiological findings. BE severity was assessed using the bronchiectasis severity index (BSI), FACED and E-FACED scores, and the bronchiectasis etiology and comorbidity index (BACI). EB was defined as a blood eosinophil count (BEC) ≥ 300 cells/μL, and T2-high EB as BEC ≥ 300 cells/μL with fractional exhaled nitric oxide (FeNO) ≥ 25 ppb. Results: Prevalence was 27% for EB and 20% for T2-high EB. EB patients exhibited poorer lung function and more severe radiologic features, with significantly higher severity scores [BSI, FACED, E-FACED, BACI (p < 0.05)], and a higher median exacerbation rate [4 (2-5) in EB vs. 2 (1-4) in non-EB, p = 0.0002], compared with non-EB patients. T2-high EB patients showed higher severity scores [BSI, FACED, E-FACED (p < 0.05)], as well as worse lung function parameters [FEV1%, FVC%, FEF 25-75% (p < 0.05)] compared with non-T2-high EB patients. In our study, patients with EB exhibited notably worsened lung function and higher BE severity scores compared with their non-EB counterparts, with exacerbations playing a major role in these differences. We found statistically significant positive correlations between BEC and disease severity scores, such as BSI, FACED, and mMRC, as well as an inverse relationship with pulmonary function. The likelihood of EB being present was significantly higher in association with mMRC ≥ 1 (OR = 2.53; 95% CI, 1.26-5.64), exacerbations/year ≥ 1 (OR = 1.27; 95% CI, 1.0-1.63), and chronic PA colonization (OR = 3.9; 95% CI, 1.08-15.8). Conclusions: EB is a distinct endotype. Dyspnea, exacerbations, and PA colonization may be predictive of EB, emphasizing the importance of early detection for improved outcomes. BEC could serve as a useful biomarker of disease severity to consider when diagnosing EB.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a frequent cause of morbidity and mortality. Dysregulated and enhanced immune-inflammatory responses have been described in COPD. Recent data showed impaired immune responses and, in particular, of interferon (IFNs) signaling pathway in these patients.
OBJECTIVE: To evaluate in peripheral lung of COPD patients, the expression of some of the less investigated key components of the innate immune responses leading to IFN productions including: IFN-receptors (IFNAR1/IFNAR2), IRF-3 and MDA-5. Correlations with clinical traits and with the inflammatory cell profile have been assessed.
METHODS: Lung specimens were collected from 58 subjects undergoing thoracic surgery: 22 COPD patients, 21 smokers with normal lung function (SC) and 15 non-smoker controls (nSC). The expression of IFNAR1, IFNAR2, IRF-3 and MDA-5, of eosinophils and activated NK cells (NKp46+) were quantified in the peripheral lung by immunohistochemistry.
RESULTS: A significant increase of IRF-3 + alveolar macrophages were observed in COPD and SC compared with nSC subjects. However, in COPD patients, the lower the levels of IRF-3 + alveolar macrophages the lower the FEV1 and the higher the exacerbation rate. The presence of chronic bronchitis (CB) was also associated with low levels of IRF-3 + alveolar macrophages. NKp46 + cells, but not eosinophils, were increased in COPD patients compared to nSC patients (p < 0.0001).
CONCLUSIONS: Smoking is associated with higher levels of innate immune response as showed by higher levels of IRF-3 + alveolar macrophages and NKp46 + cells. In COPD, exacerbation rates, severe airflow obstruction and CB were associated with lower levels of IRF-3 expression, suggesting that innate immune responses characterize specific clinical traits of the disease.

BACKGROUND: Prompt and effective management with maintenance therapy (single or dual bronchodilator therapy) is recommended after the initial diagnosis of chronic obstructive pulmonary disease (COPD) to maintain lung function and prevent exacerbations. Contrary to guideline-based recommendations, most patients are not prescribed maintenance treatment at initial diagnosis. The current study assessed the pharmacologic treatment patterns and outcomes of newly diagnosed patients with COPD in the USA.
METHODS: This retrospective, noninterventional study used de-identified data from the Inovalon Insights\' database (Commercial, Medicaid Managed Care, and Medicare Advantage-insured individuals) between January 1, 2015, and December 31, 2021. The \"patient journey\" from initial diagnosis was followed over a 4-year period. The primary outcome measure was the number of moderate or severe exacerbations. Secondary outcome measures included the cumulative incidence of exacerbations, mean cumulative count of moderate and severe exacerbations, rates of moderate and severe exacerbations in patients who remained untreated after diagnosis in 12-month time periods for 4 years, sociodemographic and clinical characteristics, and pharmacologic treatment patterns.
RESULTS: The cohort consisted of 238,158 newly diagnosed patients with COPD (female [52.9%]; mean age 63.8 years). The majority of patients with COPD had Medicaid as their primary insurance (46.2%). Overall, during the 4-year follow-up period, 32.9% of the patients had at least one moderate or severe exacerbation, and 25.8% and 13.8% experienced moderate and severe exacerbations, respectively. At diagnosis, 86.2% of the patients were untreated and most remained untreated by the end of the follow-up (63.8%). Most patients (62.0%) received long-acting beta-agonist (LABA)/inhaled corticosteroids (ICS) as their initial treatment at diagnosis, and LABA/ICS continued to be the most common initial treatment during the 4-year period (64.0% at year 1; 58.0% at year 4).
CONCLUSIONS: Most patients with COPD were not treated at initial diagnosis and remained untreated during follow-up. Our data highlight a lack of adherence to recommendations for clinical practice.

Background/Objectives: Cystic fibrosis is a genetically determined disease that significantly influences and shortens life. Treatment with CFTR modulators (CFTR-T) is a new hope for patients. It can change the predictive values of a poor prognosis (e.g., exacerbation rate and FEV1 value). The aim of the study was to analyse exacerbation incidence and spirometry data before and after one year (+/- 2 weeks) of CFTR-T in 85 CF patients at the CF Centre in Poznań. To our knowledge, this is the first analysis of CFTR-T efficiency in the Central-Eastern Europe population. Methods: We retrospectively analysed the spirometry and exacerbation data of 85 CF adult patients (both men and women), who in the middle of 2022 began treatment with CFTR modulators. Results: The one-year ratio of hospitalisation caused by severe exacerbations lowered from 1.25 to 0.21 per patient per year. We also saw a 66% decline in ambulatory exacerbations. The median FEV1% increased by 9.60% in absolute values and by 460 mL. Even in the group with very severe obstruction (FEV1 < 35%), there was an increase in median FEV1% of 5.9 in absolute values. We also proved the increase in FVC% (median 17.10% in absolute value and 600 mL) in the study group. Conclusions: After one year of treatment, an impressive improvement was observed in two important predictive values of poor prognosis: exacerbation rate and FEV1 values. Further observation is needed to determine how long the improvement will be present and its influence on quality of life and life expectancy.

UNASSIGNED: The effectiveness of different combinations of inhaled corticosteroid (ICS) therapies in reducing severe exacerbations of adult asthma remains unclear.
UNASSIGNED: This network meta-analysis (NMA) extensively evaluated the treatment effects of single ICS; dual ICS i.e., ICS/long-acting β2-adrenergic agonists (LABA); ICS/LABA as single maintenance and reliever therapy (SMART); and triple ICS, i.e., ICS/LABA/long-acting muscarinic antagonists (LAMA) in preventing severe asthma exacerbations.
UNASSIGNED: A systematic search of English databases, including PubMed and Web of Science, was conducted until December 31, 2022, using PRISMA-NMA.
UNASSIGNED: Using the PICOS criteria, the questions for this study were carefully selected so that the correct keywords could be identified.
UNASSIGNED: A pairwise meta-analysis was used to select trials based on the criteria for minimizing heterogeneity (I2). Subsequently, the \"BUGSnet\" package of R software was used to perform a Bayesian network meta-analysis.
UNASSIGNED: The main outcome measures were risk rate and annualized rate ratio of severe asthma exacerbations.
UNASSIGNED: This review included 56 randomized control trials (RCTs; n = 78,171 patients). As the pairwise meta-analysis demonstrated that the annualized rate ratio of severe asthma exacerbation had moderate heterogeneity, we analyzed the risk rate of severe asthma exacerbation using a network meta-analysis. In terms of direct/indirect comparisons with non-ICS, single ICS, dual ICS, SMART, and triple ICS reduced severe asthma exacerbations by 34 %, 47 %, 58 %, and 57 %, respectively. SMART and triple ICS showed high effectiveness in reducing severe exacerbations.
UNASSIGNED: AND RELEVANCE: SMART and triple ICS were ranked higher in effectiveness in reducing severe asthma exacerbations in comparison with other therapies, indicating that these are the most effective treatments for reducing the future risk of severe asthma exacerbations.

UNASSIGNED: Inhaled corticosteroid (ICS) therapy has been demonstrated to reduce the risk of COPD exacerbations. It should only be prescribed to COPD patients who are not adequately controlled by dual long-acting bronchodilator therapy and who have ≥2 exacerbations per year and a blood eosinophil count ≥300cells/µL. ICS therapy is widely prescribed outside guidelines to COPD patients, making ICS withdrawal an important consideration. This systematic review aims to provide an up-to-date analysis of the effect of ICS withdrawal on exacerbation frequency, change in lung function (FEV1) and to determine the proportion of COPD patients who resume ICS therapy following withdrawal.
UNASSIGNED: Randomised controlled trials (RCTs) and observational studies which compared ICS withdrawal with ICS continuation treatment were included. Cochrane Central, Web of Science, CINHAL, Embase and OVID Medline were searched. Risk of bias was assessed using the Cochrane RoB2 tool and the Newcastle-Ottawa Scale. Quality assessment of RCTs was conducted using GRADE. Meta-analysis of post-hoc analyses of RCTs of ICS withdrawal, stratified by blood eosinophil count (BEC), was undertaken.
UNASSIGNED: Ten RCTs (6642 patients randomised) and 6 observational studies (160,029 patients) were included in the results. When ICS was withdrawn and long-acting bronchodilator therapy was maintained, there was no consistent difference in exacerbation frequency or lung function change between the ICS withdrawal and continuation trial arms. The evidence for these effects was of moderate quality. There was insufficient evidence to draw a firm conclusion on the proportion of patients who resumed ICS therapy following withdrawal (estimated range 12-93% of the participants).
UNASSIGNED: Withdrawal of ICS therapy from patients with COPD is safe and feasible but should be accompanied by maintenance of bronchodilation therapy for optimal outcomes.

Clinical benefit of Alpha1-Proteinase Inhibitor (Human) (A1-PI) products for Alpha1-antitrypsin deficiency (AATD) is uncertain, based on a systematic review of observational studies and randomized controlled trials (RCTs) in AATD of Alpha1-Proteinase Inhibitor (Human) (A1-PI) products. At the recommended dose, A1-PI products raise its serum concentration but do not normalize levels. Observational studies suggest A1-PI might modestly slow progression of airflow limitation in patients with intermediate airflow obstruction, a finding not confirmed by three placebo-controlled RCTs of limited power, which showed non-significant rates of forced expiratory volume in 1 s (FEV1) change favoring placebo. These RCTs found trends favoring A1-PI in loss of high-resolution computerized tomographic (HRCT) lung density. While two meta-analyses of HRCT lung density change in RCTs achieved significance favoring A1-PI arms, clinical benefit remains uncertain. HRCT lung density measurements don\'t distinguish changes in measured density due to fluid shifts into and out of the lungs and changes in lung inflammation from those due to progressive loss of alveolar mass. A meta-analysis of RCTs found exacerbations significantly increased in A1-PI groups compared to placebo. No RCTs have shown favorable effects of A1-PI on mortality, FEV1, 6-min walking distance, quality of life, change in diffusion capacity of carbon monoxide (DLCO), or exacerbation frequency. A fourth RCT comparing two dose regimens of A1-PI is underway. RCTs have not provided evidence of clinical benefit in terms of how patients feel, function, or survive. Results have implications for the design of future clinical trials of A1-PI and potentially other products targeting AATD-associated emphysema.

Initial chronic obstructive lung disease (COPD) pharmacotherapy is based on symptom burden and exacerbation history. Inclusion of inhaled cortico-steroids (ICS) is recommended only for those with a history of exacerbations. This brief report highlights that among individuals with previously unrecognized COPD about 1 in 5 have one or more exacerbation-like events and about 1 in 10 have two or more events in the prior 12 months whether or not they self-report concomitant asthma. Closer attention to prior exacerbation-like event history might lead to more guideline concordant care. In addition, there are two other groups that have impaired but non-obstructive spirometry, some with significant respiratory symptom burden who have frequencies of exacerbation-like events similar to those meeting COPD spirometry criteria. To date we have little guidance for treatment of these individuals.

UNASSIGNED: There were substantial reductions in asthma exacerbations during the COVID-19 pandemic for reasons that remain poorly understood. We investigated changes in modifiable risk factors which might help explain the reductions in asthma exacerbations.
UNASSIGNED: Multilevel generalised linear mixed models were fitted to examine changes in modifiable risk factors for asthma exacerbations during 2020-2022, compared to pre-pandemic year (2019), using observational, routine data from general practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre. Asthma exacerbations were defined as any of GP recorded: asthma exacerbations, prescriptions of prednisolone, accident and emergency department attendance or hospitalisation for asthma. Modifiable risk factors of interest were ownership of asthma self-management plan, asthma annual review, inhaled-corticosteroid (ICS) prescriptions, influenza vaccinations and respiratory-tract-infections (RTI).
UNASSIGNED: Compared with 2019 (n = 550,995), in 2020 (n = 565,956) and 2022 (n = 562,167) (p < 0.05): asthma exacerbations declined from 67.1% to 51.9% and 61.1%, the proportion of people who had: asthma exacerbations reduced from 20.4% to 15.1% and 18.5%, asthma self-management plans increased from 28.6% to 37.7% and 55.9%; ICS prescriptions increased from 69.9% to 72.0% and 71.1%; influenza vaccinations increased from 14.2% to 25.4% and 55.3%; current smoking declined from 15.0% to 14.5% and 14.7%; lower-RTI declined from 10.5% to 5.3% and 8.1%; upper-RTI reduced from 10.7% to 5.8% and 7.6%. There was cluster effect of GP practices on asthma exacerbations (p = 0.001). People with asthma were more likely (p < 0.05) to have exacerbations if they had LRTI (seven times(x)), had URTI and ILI (both twice), were current smokers (1.4x), PPV vaccinated (1.3x), seasonal flu vaccinated (1.01x), took ICS (1.3x), had asthma reviews (1.09x). People with asthma were less likely to have exacerbations if they had self-management plan (7%), and were partially (4%) than fully COVID-19 vaccinated.
UNASSIGNED: We have identified changes in modifiable risk factors for asthma exacerbation that need to be maintained in the post-pandemic era.
UNASSIGNED: Asthma UK Centre for Applied Research and Health Data Research UK.