Currently, and based on the development of relevant biologic therapies, T2-high is the most well-defined endotype of asthma. Although much progress has been made in elucidating T2-high inflammation ...pathways, no specific clinically applicable biomarkers for T2-low asthma have been identified. The therapeutic approach of T2-low asthma is a problem urgently needing resolution, firstly because these patients have poor response to steroids, and secondly because they are not candidates for the newer targeted biologic agents. Thus, there is an unmet need for the identification of biomarkers that can help the diagnosis and endotyping of T2-low asthma.
Ongoing investigation is focusing on neutrophilic airway inflammation mediators as therapeutic targets, including interleukin (IL)-8, IL-17, IL-1, IL-6, IL-23 and tumour necrosis factor-α; molecules that target restoration of corticosteroid sensitivity, mainly mitogen-activated protein kinase inhibitors, tyrosine kinase inhibitors and phosphatidylinositol 3-kinase inhibitors; phosphodiesterase (PDE)3 inhibitors that act as bronchodilators and PDE4 inhibitors that have an anti-inflammatory effect; and airway smooth muscle mass attenuation therapies, mainly for patients with paucigranulocytic inflammation.
This article aims to review the evidence for noneosinophilic inflammation being a target for therapy in asthma; discuss current and potential future therapeutic approaches, such as novel molecules and biologic agents; and assess clinical trials of licensed drugs in the treatment of T2-low asthma.
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide accompanied by a substantial social and economic burden for the patient and the society. Poor ...sleep quality among COPD patients is frequently unnoticed and unaddressed by physicians and patients themselves, although it is a major source of further deterioration of these patients' quality of life. The aim of the present study was to record the quality of sleep in COPD patients among the Greek population and correlate these findings with various features of these patients, using the COPD and Asthma Sleep Impact Scale (CASIS). This was a cross-sectional observational study. Forty different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, CASIS questionnaire results, COPD assessment test, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, inhaled COPD treatment report) were collected from 3454 nation-wide COPD patients (Greece). The study sample consisted of COPD patients, mainly male (73%) with a median age of 69 years and a median BMI of 27.2. More than half of COPD patients (60.6%) suffered from moderate disease severity and 23.8% from severe disease, while less than half (42.1%) suffered from at least one exacerbation of the disease over the last year prior study enrollment. About 14% reported frequent to very frequent issues affecting their sleep quality, between a fourth and a third of them reported occasional night sleep disturbances, and at least half of them reported no or very infrequent problems in their night sleep. Our study indicates that the COPD assessment test (CAT) and the spirometry-based disease severity can predict the poorness in the quality of sleep (F
= 1397.5, p < 0.001, adj. R2 = 0.45) as assessed by CASIS score, and that the latter also correlates with age (ρ = 0.122, p < 0.001) and disease duration (ρ = 0.104, p < 0.001). On the contrary, there appears to be no correlation between sleep quality and number of exacerbations. Finally, untreated patients with COPD suffer from poorer quality of sleep compared to treated subjects, independently of the use of inhaled corticosteroids (F
= 21.65, p < 0.001). The results of the SLEPICO study show that increased age, prolonged disease duration, and especially CAT score ≥ 10, and severe COPD stage, might act as important indicators for deterioration in the quality of sleep, with potential consequences in the daily routine of those patients, thus urging potentially for further pharmacological interventions or modifications.
Six biologic agents are now approved for patients with severe asthma. This meta-analysis aimed to assess the efficacy and safety of licensed biologic agents in patients with severe asthma, including ...the recently approved tezepelumab.
We searched MEDLINE, Embase and CENTRAL to identify randomised controlled trials involving licensed biologics until 31 January 2023. We used random-effects meta-analysis models for efficacy, including subgroup analyses by individual agents and markers of T2-high inflammation (blood eosinophils and fractional exhaled nitric oxide), and assessed safety.
48 studies with 16 350 patients were included in the meta-analysis. Biologics were associated with a 44% reduction in the annualised rate of asthma exacerbations (rate ratio 0.56, 95% CI 0.51-0.62) and 60% reduction of hospitalisations (rate ratio 0.40, 95% CI 0.27-0.60), a mean increase in the forced expiratory volume in 1 s of 0.11 L (95% CI 0.09-0.14), a reduction in asthma control questionnaire by 0.34 points (95% CI -0.46--0.23) and an increase in asthma quality of life questionnaire by 0.38 points (95% CI 0.26-0.49). There was heterogeneity between different classes of biologics in certain outcomes, with overall greater efficacy in patients with T2 inflammation. Overall, biologics exhibited a favourable safety profile.
This comprehensive meta-analysis demonstrated that licensed asthma biologics reduce exacerbations and hospitalisations, improve lung function, asthma control and quality of life, and limit the use of systemic corticosteroids, with a favourable safety profile. These effects are more prominent in patients with evidence of T2 inflammation.
Assessment of clinical outcomes in the real-world corroborates findings from randomized controlled trials (RCTs).
This meta-analysis evaluated real-world data of omalizumab on treatment response, ...lung function, exacerbations, oral corticosteroid (OCS) use, patient-reported outcomes (PROs), health care resource utilization (HCRU), and school/work absenteeism at 4, 6, and 12 months after treatment.
Observational studies in patients with severe allergic asthma (≥6 years) treated with omalizumab for ≥16 weeks, published from January 2005 to October 2018, were retrieved from PubMed, Embase, and Cochrane. A random-effects model was used to assess heterogeneity.
In total, 86 publications were included. Global evaluation of treatment effectiveness (GETE) was good/excellent in 77% patients at 16 weeks (risk difference: 0.77; 95% confidence interval CI: 0.70-0.84; I2 = 96%) and in 82% patients at 12 months (0.82, 0.73-0.91; 97%). The mean improvement in forced expiratory volume in 1 second was 160, 220, and 250 mL at 16 weeks, 6 months, and 12 months, respectively. There was a decrease in Asthma Control Questionnaire score at 16 weeks (−1.14), 6 months (−1.56), and 12 months (−1.13) after omalizumab therapy. Omalizumab significantly reduced annualized rate of severe exacerbations (risk ratio RR: 0.41, 95% CI: 0.30-0.56; I2 = 96%), proportion of patients receiving OCS (RR: 0.59, 95% CI: 0.47-0.75; I2 = 96%), and number of unscheduled physician visits (mean difference: −2.34, 95% CI: −3.54 to −1.13; I2 = 98%) at 12 months versus baseline.
The consistent improvements in GETE, lung function, and PROs, and reductions in asthma exacerbations, OCS use, and HCRU with add-on omalizumab in real-life confirm and complement the efficacy data of RCTs.
Chronic respiratory diseases constitute a considerable part in the practice of pulmonologists and primary care physicians; spirometry is integral for the diagnosis and monitoring of these diseases, ...yet remains underutilized. The Air Next spirometer (NuvoAir, Sweden) is a novel ultra-portable device that performs spirometric measurements connected to a smartphone or tablet via Bluetooth®.
The objective of this study was to assess the accuracy and validity of these measurements by comparing them with the ones obtained with a conventional desktop spirometer. Two hundred subjects were enrolled in the study with various spirometric patterns (50 patients with asthma, 50 with chronic obstructive pulmonary disease and 50 with interstitial lung disease) as well as 50 healthy individuals.
For the key spirometric parameters in the interpretation of spirometry, i.e. FEV
, FVC, FEV
/FVC and FEF
, Pearson correlation and Interclass Correlation Coefficient were greater than 0.94, exhibiting perfect concordance between the two spirometers. Similar results were observed in an exploratory analysis of the subgroups of patients. Using Bland-Altman plots we have shown good reproducibility in the measurements between the two devices, with small mean differences for the evaluated spirometric parameters and the majority of measurements being well within the limits of agreement.
Our results support the use of Air Next as a reliable spirometer for the screening and diagnosis of various spirometric patterns in clinical practice.
Idiopathic Pulmonary Fibrosis (IPF) represents a chronic lung disease with unpredictable course.
We aimed to investigate prognostic performance of complete blood count parameters in IPF. ...Treatment-naïve patients with IPF were retrospectively enrolled from two independent cohorts (derivation and validation) and split into subgroups (high and low) based on median baseline monocyte count and red cell distribution width (RDW).
Overall, 489 patients (derivation cohort: 300, validation cohort: 189) were analyzed. In the derivation cohort, patients with monocyte count ≥ 0.60 K/μL had significantly lower median FVC%pred 75.0, (95% CI 71.3-76.7) vs. 80.9, (95% CI 77.5-83.1), (P = 0.01) and DLCO%pred 47.5, (95% CI 44.3-52.3) vs. 53.0, (95% CI 48.0-56.7), (P = 0.02) than patients with monocyte count < 0.60 K/μL. Patients with RDW ≥ 14.1% had significantly lower median FVC%pred 75.5, (95% CI 71.2-79.2) vs. 78.3, (95% CI 76.0-81.0), (P = 0.04) and DLCO%pred 45.4, (95% CI 43.3-50.5) vs. 53.0, (95% CI 50.8-56.8), (P = 0.008) than patients with RDW < 14.1%. Cut-off thresholds from the derivation cohort were applied to the validation cohort with similar discriminatory value, as indicated by significant differences in median DLCO%pred between patients with high vs. low monocyte count 37.8, (95% CI 35.5-41.1) vs. 45.5, (95% CI 41.9-49.4), (P < 0.001) and RDW 37.9, (95% CI 33.4-40.7) vs. 44.4, (95% CI 41.5-48.9), (P < 0.001). Patients with high monocyte count and RDW of the validation cohort exhibited a trend towards lower median FVC%pred (P = 0.09) and significantly lower median FVC%pred (P = 0.001), respectively. Kaplan-Meier analysis in the derivation cohort demonstrated higher all-cause mortality in patients with high (≥ 0.60 K/μL) vs. low monocyte count (< 0.60 K/μL) HR 2.05, (95% CI 1.19-3.53), (P = 0.01).
Increased monocyte count and RDW may represent negative prognostic biomarkers in patients with IPF.
Abstract
Context: Electronic cigarettes (e-cigarettes) are becoming increasingly popular yet their effects on health remain unknown.
Objective: To conduct the first comprehensive and standardized ...assessment of the acute impact of active and passive e-cigarette smoking on serum cotinine and lung function, as compared to active and passive tobacco cigarette smoking.
Materials and methods: Fifteen smokers ( 15 cigarettes/day; seven females; eight males) and 15 never-smokers (seven females; eight males) completed this repeated-measures controlled study. Smokers underwent a control session, an active tobacco cigarette (their favorite brand) smoking session and an active e-cigarette smoking session. Never-smokers underwent a control session, a passive tobacco cigarette smoking session and a passive e-cigarette smoking session. Serum cotinine, lung function, exhaled carbon monoxide and nitric oxide were assessed. The level of significance was set at p 0.001 to adjust for multiple comparisons.
Results: e-Cigarettes and tobacco cigarettes generated similar (p > 0.001) effects on serum cotinine levels after active (60.6 ± 34.3 versus 61.3 ± 36.6 ng/ml) and passive (2.4 ± 0.9 versus 2.6 ± 0.6 ng/ml) smoking. Neither a brief session of active e-cigarette smoking (indicative: 3% reduction in FEV1/FVC) nor a 1 h passive e-cigarette smoking (indicative: 2.3% reduction in FEV1/FVC) significantly affected the lung function (p > 0.001). In contrast, active (indicative: 7.2% reduction in FEV1/FVC; p < 0.001) but not passive (indicative: 3.4% reduction in FEV1/FVC; p = 0.005) tobacco cigarette smoking undermined lung function.
Conclusion: Regarding short-term usage, the studied e-cigarettes generate smaller changes in lung function but similar nicotinergic impact to tobacco cigarettes. Future research should target the health effects of long-term e-cigarette usage, including the effects of nicotine dosage.
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