Alpha‐1 antitrypsin deficiency is an autosomal, codominant disorder caused by mutations of the SERPINA1 gene. Several mutations of SERPINA1 have been described associated with the development of ...pulmonary emphysema and/or chronic liver disease and cirrhosis. Here, we report a very rare PI*Q0parma variant identified for the first time in an Italian family originally from the city of Parma in Northern Italy
Here, we report a very rare PI*Q0parma variant identified for the first time in an Italian family originally from the city of Parma in Northern Italy.
Factors determining the shape of the human rib cage are not completely understood. We aimed to quantify the contribution of anthropometric and COPD-related changes to rib cage variability in adult ...cigarette smokers.
Rib cage diameters and areas (calculated from the inner surface of the rib cage) in 816 smokers with or without COPD, were evaluated at three anatomical levels using computed tomography (CT). CTs were analyzed with software, which allows quantification of total emphysema (emphysema%). The relationship between rib cage measurements and anthropometric factors, lung function indices, and %emphysema were tested using linear regression models.
A model that included gender, age, BMI, emphysema%, forced expiratory volume in one second (FEV1)%, and forced vital capacity (FVC)% fit best with the rib cage measurements (R(2) = 64% for the rib cage area variation at the lower anatomical level). Gender had the biggest impact on rib cage diameter and area (105.3 cm(2); 95% CI: 111.7 to 98.8 for male lower area). Emphysema% was responsible for an increase in size of upper and middle CT areas (up to 5.4 cm(2); 95% CI: 3.0 to 7.8 for an emphysema increase of 5%). Lower rib cage areas decreased as FVC% decreased (5.1 cm(2); 95% CI: 2.5 to 7.6 for 10 percentage points of FVC variation).
This study demonstrates that simple CT measurements can predict rib cage morphometric variability and also highlight relationships between rib cage morphometry and emphysema.
In this study, we tested the association between COPD and interstitial lung abnormality (ILA), notably in relation to the presence of computed tomography (CT) signs of lung fibrosis.
COPD cases were ...selected from participants undergoing lung cancer screening (Multicentric Italian Lung Detection trial) for airflow obstruction (n=311/2,303, 13.5%) and 146 consecutive patients with clinical COPD. In all, 457 COPD cases were selected and classified according to the stages of Global Initiative for Chronic Obstructive Lung Disease. A nested matching (case:control = 1:2) according to age, sex, and smoking history was operated between each COPD case and two control subjects from Multicentric Italian Lung Detection trial without airflow obstruction. Low-dose CT scans of COPD cases and controls were reviewed for the presence of ILA, which were classified into definite or indeterminate according to the presence of signs of lung fibrosis.
The frequency of definite ILA was similar between COPD cases and controls (P=0.2), independent of the presence of signs of lung fibrosis (P=0.07). Combined definite and indeterminate ILA was homogeneously distributed across Global Initiative for Chronic Obstructive Lung Disease stages (P=0.6). Definite ILA was directly associated with current smoker status (odds ratio OR 4.05, 95% confidence interval CI: 2.2-7.4) and increasing pack-years (OR 1.01, 95% CI: 1-1.02). Subjects with any fibrotic ILA were more likely to be older (OR 1.17, 95% CI: 1.10-1.25) and male (OR 8.58, 95% CI: 1.58-68.9).
There was no association between COPD and definite ILA. However, low-dose CT signs of lung fibrosis were also observed in COPD, and their clinical relevance is yet to be determined.
Background There is increasing evidence to support a role for total mast cells (MCTOT ) in the vascular component of airway remodeling in asthma. On the contrary, up to now, no study has addressed ...the role of chymase-positive mast cells (MCTC ) in microvasculature changes. Objective We sought to assess the role of MCTC in the vascular component of airway remodeling in asthma. Methods We recruited 8 patients with mild-to-moderate asthma and 8 healthy volunteers as a control group. Fiberoptic bronchoscopy with endobronchial biopsy was successfully performed in all subjects. Immunostaining was performed for quantification of vessels, vascular endothelial growth factor (VEGF)–positive cells, MCTOT , and MCTC. Results Compared with those from healthy subjects, endobronchial biopsy specimens from asthmatic patients showed increased numbers of MCTOT and MCTC and VEGF+ cells ( P < .05). In asthmatic patients the number of vessels and the vascular area was also greater than in healthy subjects ( P < .05). Additionally, in asthmatic patients the number of MCTC was significantly related to the vascular area ( rs = 0.74, P < .01) and to the number of VEGF+ cells ( rs = 0.78, P < .01). Moreover, a colocalization study revealed that MCTC were a relevant cellular source of VEGF. Finally, a 6-week treatment with inhaled fluticasone propionate was able to reduce MCTC numbers. Conclusion MCTC can play a role in the vascular component of airway remodeling in asthma, possibly through induction of VEGF. Clinical implications Specific targeting of MCTC might be a tool for treating vascular remodeling in asthma.
In chronic obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), changes in bronchial microvasculature are present in response to inflammatory stimuli. ...Vascular changes may significantly contribute to airway wall remodelling. Angiogenesis and vascular leakage are prevalent in asthma, while vasodilation and vascular leakage dominate in COPD. An endothelial dysfunction may be present both in asthma and in COPD. Vascular changes may occur simultaneously with the thickening of the airway wall and the narrowing of the bronchial lumen. Consequently, pharmacological control of bronchial vascular remodelling may be crucial for symptom control in asthma and COPD. In asthmatic airways, inhaled steroids can downregulate vascular remodelling by acting on proangiogenic factors. Additionally, studies on combination therapy with long-acting β2-agonists and inhaled steroids have provided evidence of a possible synergistic action on components of vascular remodelling in asthma. In COPD, there is less experimental evidence on the effect of inhaled steroids on airway microvascular changes. Importantly, vascular endothelial growth factor (VEGF), the most specific growth factor for vascular endothelium, is crucially involved in the pathophysiology of airway vascular remodelling, both in asthma and COPD. The inhibition of VEGF and its receptor may be useful in the treatment of the vascular changes in the airway wall.
ABSTRACT
The human organism is inhabited by trillions of microorganisms, known as microbiota, which are considered to exploit a pivotal role in the regulation of host health and immunity. Recent ...investigations have suggested a relationship between the composition of the human microbiota and COVID-19 infection, highlighting a possible role of bacterial communities in the modulation of the disease severity. In this study, we performed a shotgun metagenomics analysis to explore and compare the nasopharyngeal microbiota of 38 hospitalized Italian patients with and without COVID-19 infection during the third and fourth pandemic waves. In detail, the metagenomic analysis combined with specific correlation analyses suggested a positive association of several microbial species, such as
S. parasanguinis
and
P. melaninogenica
, with the severity of COVID-19 infection. Furthermore, the comparison of the microbiota composition between the nasopharyngeal and their respective fecal samples highlighted an association between these different compartments represented by a sharing of several bacterial species. Additionally, lipidomic and deep-shotgun functional analyses of the fecal samples suggested a metabolic impact of the microbiome on the host’s immune response, indicating the presence of key metabolic compounds in COVID-19 patients, such as lipid oxidation end products, potentially related to the inflammatory state. Conversely, the patients without COVID-19 displayed enzymatic patterns associated with the biosynthesis and degradation of specific compounds like lysine (synthesis) and phenylalanine (degradation) that could positively impact disease severity and contribute to modulating COVID-19 infection.
IMPORTANCE
The human microbiota is reported to play a major role in the regulation of host health and immunity, suggesting a possible impact on the severity of COVID-19 disease. This preliminary study investigated the possible correlation between nasopharyngeal microbiota and COVID-19 infection. In detail, the analysis of the nasopharyngeal microbiota of hospitalized Italian patients with and without COVID-19 infection suggested a positive association of several microbial species with the severity of the disease and highlighted a sharing of several bacteria species with the respective fecal samples. Moreover, the metabolic analyses suggested a possible impact of the microbiome on the host's immune response and the disease severity.
The human microbiota is reported to play a major role in the regulation of host health and immunity, suggesting a possible impact on the severity of COVID-19 disease. This preliminary study investigated the possible correlation between nasopharyngeal microbiota and COVID-19 infection. In detail, the analysis of the nasopharyngeal microbiota of hospitalized Italian patients with and without COVID-19 infection suggested a positive association of several microbial species with the severity of the disease and highlighted a sharing of several bacteria species with the respective fecal samples. Moreover, the metabolic analyses suggested a possible impact of the microbiome on the host's immune response and the disease severity.
The airways smaller than 2 mm diameter are named small airways. They are essential for the transport and exchange of oxygen and carbon dioxide and at the same time play a relevant role in pulmonary ...mechanics, contributing to the subdivision of lung volumes. Measurement of small airway function is, therefore, crucial in patients with respiratory disease. This overview focuses on the physiological aspects of the small airways, considered as air ducts as well as determinants of pulmonary mechanics, the most common tools for evaluating their function and treatment implications.
Airways remodeling, evaluated as the subepithelial layer thickness, was compared in asthmatic patients with that of healthy subjects, and was related to clinical grading of disease, presence of ...atopy, and length of asthmatic history.
Thirty-four patients with stable asthma (mean age±SD: 26.5±9.2 years; 10 female) treated with only inhaled β2-agonists and eight healthy volunteers (mean age±SD: 24.6±2.5 years; four female) were recruited for the study. Twenty-seven of 34 asthmatics had atopy. Eleven patients had newly diagnosed conditions (duration of disease ≤1 year), nine patients had long asthmatic history (>1 year and ≤10 years), and 14 had prolonged asthmatic history (>10 years). Bronchial responsiveness to methacholine (M) was expressed as provocative concentration of M causing a 20% fall in FEV1 (PC20) (mg/mL). Degree of asthma severity was assessed using a 0- to 12-point score based on symptoms, bronchodilator use, and daily peak expiratory flow variability over a 3-week period. Bronchoscopy and bronchial biopsy were performed successfully for all subjects; the subepithelial layer thickness, in biopsy samples, was measured from the base of bronchial epithelium to the outer limit of reticular lamina.
In asthmatics, baseline FEV1 values (percent of predicted) ranged from 75.7 to 137.0%, and PC20 M ranged from 0.15 to 14.4 mg/mL. According to the asthma severity score, 14 asthmatics were classified as having mild disease, 14 as having moderate disease, and six as having severe disease. The mean values of subepithelial layer thickness were 12.4±3.3 µm (range, 6.8 to 22.1 µm) in asthmatics, and 4.4±0.5 µm (range, 3.8 to 5.2 µm) in healthy subjects (p<0.001). Subepithelial layer thickness of those with severe asthma differed significantly from that of patients with moderate and mild asthma (16.7±3.1 µm vs 12.1 ±2.7 µm and 10.8±2.4 µm, p<0.01 and p<0.003, respectively). Moreover, in asthmatics, degree of thickening was positively correlated to asthma severity score (Spearman rank correlation coefficient rs=0.581; p<0.001), and negatively correlated with baseline FEV1 (rs=—0.553; p<0.001) and PC20 M (rs=—0.510; p<0.01). No difference was found between degree of thickening observed in atopic asthmatics, compared with that of nonatopic asthmatics, or between degree of thickening in patients with different lengths of asthmatic history. Lastly, multiple regression analysis revealed that asthma severity score was the significant predictive factor for thickness of subepithelial layer.
We confirmed that airways remodeling is a very distinctive and characteristic pathologic finding of asthma. We also demonstrated that it is related to the clinical and functional severity of asthma, but not to atopy or length of asthmatic history.
Therapeutic advances in drug therapy of chronic obstructive pulmonary disease (COPD) really effective in suppressing the pathological processes underlying the disease deterioration are still needed. ...Artificial Intelligence (AI) via Machine Learning (ML) may represent an effective tool to predict clinical development of investigational agents.
Experimental drugs in Phase I and II development for COPD from early 2014 to late 2022 were identified in the ClinicalTrials.gov database. Different ML models, trained from prior knowledge on clinical trial success, were used to predict the probability that experimental drugs will successfully advance toward approval in COPD, according to Bayesian inference as follows: ≤25% low probability, >25% and ≤50% moderate probability, >50% and ≤75% high probability, and >75% very high probability.
The Artificial Neural Network and Random Forest ML models indicated that, among the current experimental drugs in clinical trials for COPD, only the bifunctional muscarinic antagonist - β
-adrenoceptor agonists (MABA) navafenterol and batefenterol, the inhaled corticosteroid (ICS)/MABA fluticasone furoate/batefenterol, and the bifunctional phosphodiesterase (PDE) 3/4 inhibitor ensifentrine resulted to have a moderate to very high probability of being approved in the next future, however not before 2025.
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