Asthma management, focused on the use of oral corticosteroids: the opinions of Italian asthmatic patients.

OBJECTIVE: Patients' perceptions of asthma symptoms, and attitudes regarding diagnosis and management, can affect their ability to reach good asthma control. The aim of the study was to explore patients' perceptions of asthma management, with focus on treatment with oral corticosteroids (OCS). METHODS: A DOXAPHARMA survey was conducted. A questionnaire with 46 multiple choice questions was completed by 50 patients with severe uncontrolled asthma, and 258 with mild-moderate controlled or partly controlled asthma. Participants were representative of Italian asthmatic patients-with medium age, long asthma duration, delayed diagnosis, poor asthma control, and frequent exacerbations. RESULTS: Many asthmatics reported inadequate pharmacologic treatment. The majority but not all patients regularly used ICS/LABA. Oral treatment was common, mainly with OCS, particularly in severe asthmatics. One-fourth of patients did not regularly use inhaled therapy, and adherence was poor, resulting in frequent OCS use to treat exacerbations, which were common in mild-moderate cases. Patients were fairly satisfied with asthma therapies, but many had concerns about long-term corticosteroid use. Patients complained about poor management of comorbidities associated with asthma and OCS use, but were generally satisfied with their patient/doctor relationships. Many patients failed to achieve optimal health-related quality of life (HRQoL), mainly those with severe asthma who used OCS treatment and emphasized how OCS therapy impacted QoL. CONCLUSIONS: The survey results confirmed many problems related to mild-moderate and severe asthma management in Italy and highlighted the overuse of OCS rather than more effective and safe treatments, which had strong negative effects on HRQoL.

Assessment of respiratory function and exercise tolerance at 4-6 months after COVID-19 infection in patients with pneumonia of different severity.

BACKGROUND: The evaluation of COVID-19 systemic consequences is a wide research field in which respiratory function assessment has a pivotal role. However, the available data in the literature are still sparse and need further strengthening. AIM: To assess respiratory function 4-6 months after hospital discharge based on lung disease severity in patients who overcome COVID-19 pneumonia. METHODS: Patients hospitalised either in the Internal Medicine Department (IMD) for moderate to severe disease or in the Intensive Care Unit (ICU) for critical disease underwent spirometry with maximal flow-volume curve, lung volumes, lung diffusion capacity (DLCO ) and six-minute walking test (6-MWT). RESULTS: Eighty-eight patients were analysed: 40 from the IMD and 48 from the ICU. In both cohorts, there was a greater prevalence of male patients. In the IMD cohort, 38% of patients showed at least one altered respiratory parameter, while 62% in the ICU cohort did so (P < 0.05). Total lung capacity (TLC) and DLCO were the most frequently altered parameters: 15% and 33% from IMD versus 33% and 56% from ICU, respectively (P < 0.05). In IMD patients, 5% had only restrictive deficit, 22% had only lung diffusion impairment and 10% had both. In ICU patients, 6% had only restrictive deficit, 29% had only lung diffusion impairment and 27% had both (P < 0.05). ICU patients showed a higher frequency of abnormal 6-MWT (P < 0.05). CONCLUSION: Lung function tests and 6-MWT are highly informative tools for monitoring the negative consequences of COVID-19 pneumonia, which were more frequent and more complex in patients discharged from ICU.

Pulmonary rehabilitation improves functional outcomes and quality of life in post-SARS-CoV-2 mild-to-moderate infection patients: a pilot study.

SARS-CoV-2 infection impairs functional outcomes and quality of life, even in its mild-to-moderate form. Therefore, it is appropriate to draw attention to the role played by respiratory rehabilitation and physiotherapists in the pulmonary rehabilitation process that post-SARS-CoV-2 patients must undergo. We enrolled 80 patients in a prospective case-control study; 40 cases (mild-to-moderate post-SARS-CoV-2 infection patients) and 38 control subjects (i.e., patients affected by other respiratory diseases) completed the same full pulmonary rehabilitation cycle. 6-minute walking distance, Borg category-ratio 10 scale, modified Medical Research Council (mMRC) dyspnea scale, European quality of life 5-dimensions-3-level (EuroQoL EQ-5D-3L) questionnaire, Barthel scale, arterial blood gas test, and peripheral oxygen saturation were compared for all patients before and after rehabilitation. All patients experienced significant improvements in all parameters analyzed, except for the arterial blood gas test. Results were similar for both groups; in particular, both groups experienced improvements in the mMRC scale, EuroQoL EQ-5D-3L questionnaire, Barthel scale, and 6-minute walking distance. Pulmonary rehabilitation appears to improve exercise tolerance, dyspnea, and quality of life in patients recovering from a mild-to-moderate SARS-CoV-2 infection. Further studies are needed on a larger sample size population to validate these results.

Effects of short-term exposure to particulate matter on emergency department admission and hospitalization for asthma exacerbations in Brescia district.

BACKGROUND: Rising pollution plays a crucial role in worsening several respiratory diseases. Particulate Matter (PM)-induced asthma exacerbations are one of the most dangerous events. OBJECTIVES: To assess the correlation between progressive particulate matter short-term exposure and asthma exacerbations, we investigated the role of PM levels on Emergency Department (ED) admissions and hospitalizations for these events in Brescia, an important industrial city located in northern Italy with high yearly levels of air pollution. METHODS: We analyzed 1050 clinical records of ED admissions for suspected asthma exacerbation, starting from January 2014 to December 2017. Daily PM levels were collected from the Environmental Protection Regional Agency. We performed a time-series analysis using a Poisson regression model with single and multiple day-lag. Results were expressed as Relative Risk (RR) and Excess of Relative Risk (ERR) of severe asthma exacerbation over a 10 µg/m3 increase in PM10 and PM2.5 concentration. RESULTS: We selected and focused our analysis on 543 admissions for indisputable asthma exacerbation in ED and hospital. The time-series study showed an increase of the RR (CI95%) for asthma exacerbation-related ED admissions of 1.24 with an ERR of 24.2% for PM2.5 at lag0-1 (p < 0.05). We also estimated for PM2.5 a RR (CI95%) of 1.12 with an ERR of 12.5% at lag0-5 (p ≤ 0.05). Again, for PM2.5, an increase of the RR (CI95%) for asthma exacerbation-related hospitalizations of 1.31 with an ERR of 30.7% at lag0-1 (p < 0.05) has been documented. These findings were confirmed and even reinforced considering only the population living in the city. CONCLUSIONS: Short-term PM exposure, especially for PM2.5, plays a critical role in inducing asthma exacerbation events leading to ED admission or hospitalization.

Mild/Moderate Asthma Network in Italy (MANI): a long-term observational study.

OBJECTIVE: The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80-90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis. Studies are needed to develop long-term, observational, real-life research in large cohorts. The primary outcomes of this study will be based on prospective observation and the epidemiological evolution of mild and moderate asthma. Secondary outcomes will include patient-reported outcomes, treatments over time, disease-related functional and inflammatory patterns, and environmental and life-style influences. METHODS: This study, called the Mild/Moderate Asthma Network of Italy (MANI), is a research initiative launched by the Italian Respiratory Society and the Italian Society of Allergology, Asthma and Clinical Immunology. MANI is a cluster-based, real world, cross-sectional, prospective, observational cohort study that includes 20,000 patients with mild-to-moderate asthma. (ClinicalTrials.gov Identifier: NCT04796844). RESULTS AND CONCLUSION: Despite advances in asthma care, several research gaps remain to be addressed through clinical research. This study will add important new knowledge about long-term disease history, the transferability of clinical research results to daily practice, the efficacy of currently recommended strategies, and their impact on the burden and evolution of the disease. ABBREVIATIONS: MANI:Mild/Moderate Asthma Network of ItalySANI:Severe Asthma Network ItalyGINA:Global Initiative for AsthmaSABA:short acting ß2-agonistsICS:inhaled corticosteroidsCRF:Case Report Form.

Acute Effect of Bronchodilator on Intrathoracic Airway Wall Compliance in COPD Patients.

PURPOSE: In patients with chronic obstructive pulmonary disease (COPD), bronchial responsiveness after acute administration of short acting bronchodilators is conventionally assessed by measuring the improvement of forced expiratory volume in the first second (FEV1) during a maximal forced expiratory maneuver. This study aimed to measure the variation of intrathoracic airway wall compliance (AWC) after acute administration of short acting beta-2 agonist in COPD patients since this might influence the final modification of airway caliber during maximal expiratory effort and the resulting bronchodilation as inferred by FEV1 changes. METHODS: In a group of 10 patients suffering from COPD, intrathoracic AWC was measured at middle (50% of Forced Vital Capacity (FVC) and low (75% of FVC) lung volumes using the interrupter method during forced expiratory maneuver in basal conditions and after acute inhalation of albuterol (salbutamol) (400 mcg by MDI). Ten healthy subjects were examined similarly as a control group. RESULTS: Lower values of baseline intrathoracic AWC at both lung volumes were found in COPD patients (1.72 ± 0.20 ml/cmH2O and 1.08 ± 0.20 ml/cmH2O, respectively) as compared to controls (2.28 ± 0.27 ml/cmH2O and 1.44 ± 0.22 ml/cmH2O, respectively) (p < 0.001). In COPD patients, AWC increased significantly at both lung volumes after salbutamol, amounting to 1.81 ± 0.38 ml/cmH2O and 1.31 ± 0.39 ml/cmH2O, respectively (p < 0.01), but the relative change was not different from that observed in controls. CONCLUSION: In COPD patients, AWC is reduced compared to controls, but after bronchodilator, the intrathoracic airways become more compliant. The consequent increased collapsibility under high positive pleural pressure could limit the airway caliber improvement seen after bronchodilator, as assessed by the FEV1 changes during the forced expiratory maneuver, underestimating the effective bronchodilation achieved in these patients.

Lung Ultrasound in Patients With SARS-COV-2 Pneumonia: Correlations With Chest Computed Tomography, Respiratory Impairment, and Inflammatory Cascade.

OBJECTIVES: Lung ultrasound (LUS) might be comparable to chest computed tomography (CT) in detecting parenchymal and pleural pathology, and in monitoring interstitial lung disease. We aimed to describe LUS characteristics of patients during the hospitalization for COVID-19 pneumonia, and to compare the extent of lung involvement at LUS and chest-CT with inflammatory response and the severity of respiration impairment. METHODS: During a 2-week period, we performed LUS and chest CT in hospitalized patients affected by COVID-19 pneumonia. Dosages of high sensitivity C-reactive protein (HS-CRP), d-dimer, and interleukin-6 (IL-6) were also obtained. The index of lung function (P/F ratio) was calculated from the blood gas test. LUS and CT scoring were assessed using previously validated scores. RESULTS: Twenty-six consecutive patients (3 women) underwent LUS 34 ± 14 days from the early symptoms. Among them, 21 underwent CT on the same day of LUS. A fair association was found between LUS and CT scores (R = 0.45, P = .049), which became stronger if the B-lines score on LUS was not considered (R = 0.57, P = .024). LUS B-lines score correlated with IL-6 levels (R = 0.75, P = .011), and the number of involved lung segments detected by LUS correlated with the P/F ratio (R = 0.60, P = .019) but not with HS-CRP and d-Dimer levels. No correlations were found between CT scores and inflammations markers or P/F. CONCLUSION: In patients with COVID-19 pneumonia, LUS was correlated with both the extent of the inflammatory response and the P/F ratio.

Home-based pulmonary rehabilitation in patients undergoing (chemo)radiation therapy for unresectable lung cancer: a prospective explorative study.

AIMS: The prevention of pulmonary toxicity is an important goal for patient candidate to radiation therapy for lung cancer. There is a lack of evidence on the role of exercise training for patients with unresectable stage III lung cancer candidated to radical treatment. The aim of this study was to evaluate the feasibility of a home-based pulmonary rehabilitation (PR) program and to identify reliable tools in terms of respiratory function, exercise capacity and quality of life. METHODS: Patients' recruitment lasted from April 2020 till February 2022. The PR program was proposed concomitantly to radiation therapy to the first 20 patients (interventional group, IG), and the other 20 patients were identified as an observational group (OG). All patients were assessed at baseline (T0) and after 8 weeks (T2) with 6 minute walking test (6MWT), modified Borg Scale (mBORG), SF-36 questionnaire (SF-36) and pulmonary function test (PFT); after 4 weeks (T1), only SF-36 was administered. RESULTS: A decrease of 13.8 m in the walked-distance was registered in the OG between T0 and T2 (p = 0.083). Instead, an increase of 56.6 m in the distance walked was recorded in the IG between T0 and T2 (p ≤ 0.001). In the OG, the mBORG scores showed a negative trend. On the contrary, in the IG, these scores showed a slight improvement. In the OG, all the items of SF-36 scores decreased between T0 and T1. In the IG, an increased trend from T0 to T2 was observed for all the items of SF-36. No clinically significant variations were detected from baseline to T2 in both groups regarding PFT. CONCLUSION: The 6MWT, mBORG and SF-36 resulted as useful tools to assess the role of a PR program. A significant gain in functional exercise capacity and a prevention of the physiological impairment of QoL during radio(chemo)therapy was registered.

Regulatory T cell monitoring in severe eosinophilic asthma patients treated with mepolizumab.

Severe eosinophilic asthma (SEA) has been associated with T-helper type 2 (Th2) inflammatory response. A good understanding of T cell functions in asthma is important for therapy, especially in the choice of biological treatments for severe cases. Mepolizumab, an IL-5 antagonist, is indicated for the treatment of severe asthma. Regulatory T cells (Tregs) suppress inflammation by secreting cytokines that inhibit Th2 cell proliferation. We investigated peripheral Treg, CD4, CD8, CD19 and NK cell percentages and their relationship to clinical and functional parameters, including peripheral eosinophils, before and after anti-IL5 treatment. Subjects were 14 adult SEA patients (9 male, 54.1 ± 11.6 years), treated with mepolizumab, and 10 controls. T cells (CD4 and CD8), CD19, NK and Tregs were evaluated by flow cytometry. Comparison of lung function parameters before and after treatment with mepolizumab (T0 and T1) showed an increase in FEV1, FEV1/FVC ratio and a reduction in blood eosinophil percentages. CD8 and CD16/56+ CD3+ were significantly higher in SEA patients than controls (P = .04 and P = .03, respectively). A decrease in CD45+, CD8 + and CD16/56+ CD3+ cell percentages was observed between T0 and T1 (P = .02, P = .04, P = .03, respectively). A significant increase in Treg percentages (P = .0001) was recorded between T0 and T1. Mepolizumab therapy was found to modulate immune response, restoring immune balance in patients with SEA.

Investigating the Link between Alpha-1 Antitrypsin Deficiency and Abdominal Aortic Aneurysms.

BACKGROUND: Alpha-1-Antitrypsin (AAT) is one of the major plasmatic protease inhibitors. In the last decade, an association between Alpha-1-Antitrypsin Deficiency (AATD) and Abdominal Aortic Aneurysms (AAA) has been hypothesized. Multiple factors may be involved in AAA's etiopathogenesis, and an underlying structural defect of the extracellular matrix (ECM) is always present. AATD could be a reasonable risk factor for AAA because it is related to protease/antiprotease imbalance and enhanced ECM degradation of the vessel wall. METHODS: We performed genotyping of 138 patients hospitalized in the Vascular Surgery Division of the ASST-Spedali Civili di Brescia, Italy, for nontraumatic rupture of AAA. The second purpose was to observe the distribution of main nongenetic risk factors for AAA between patients with and without AATD. RESULTS: Out of 138 patients, 22 were found with AATD: 16 MS, 1 SS, 3 MZ, and 2 with a new rare AAT variant. When compared to the general Italian population, our cohort's frequency of deficient S allele was significantly higher (7.8 vs. 2.2% respectively, P < 0.01), whereas the deficient Z allele was similar (1.1 vs. 1.3% respectively, P > 0.05). Although we found no differences in age, gender, hypertension, diabetes, and smoke habits between AAA patients with and without AATD, hyperlipidemia was significantly less frequent in patients with AATD (46.4 vs. 12.5% respectively, P < 0.05). CONCLUSIONS: In our AAA patients' cohort, the S allele frequency was higher than in the general Italian population. Our results support the hypothesis that AATD might be a risk factor for AAA.

Z-alpha1-antitrypsin polymers and small airways disease: a new paradigm in alfa-1 anti-trypsin deficiency-related COPD development?

The presence of Alpha1-Antitrypsin (AAT) polymers, known to promote a sustained pro-inflammatory activity, has been previously demonstrated in bronchial biopsies of subjects with Z-AAT deficiency (AATD) suggesting a possible role in the development of COPD through a small airway disease impairment. The study aimed to assess the presence of small airways dysfunction and the potential correlation with the presence of Z-AAT polymers obtained by Exhaled Breath Condensate (EBC) collection in PiZZ subjects, as compared with matched healthy PiMM subjects. We enrolled 19 asymptomatic, never smoker subjects: 9 PiZZ and 10 PiMM as controls, without obstructive ventilatory defect (i.e., normal FEV1/VC% ratio). All subjects underwent complete pulmonary function tests (PFT). EBC was collected in all subjects. ELISA test was applied to search for Z-AAT polymers. The PiZZ subjects showed normal lung volumes and DLCO values. However, in comparison with PiMM subjects, the single breath test N2 wash-out revealed significant differences regarding the phase III slope (1.45±0.35 N2/L vs. 0.96±0.40 N2/L) (p<0.02) in the PiZZ subjects, while the closing volume/vital capacity ratio (14.3±4.5 % vs. 11.3±6.3 %) was not significantly increased. The ELISA test detected the presence of Z-AAT polymers in 44% of PiZZ patients. Asymptomatic, never smoker PiZZ subjects with normal spirometry and lung diffusion capacity showed airways impairment when compared to PiMM subjects. Although Z-AAT polymers were found only in 44% of PiZZ subjects, these findings suggest the possibility that chronic bronchiolitis can develop as a result of the long-term pro-inflammatory activity of Z-AAT polymers in subjects with Z-related AATD.

Effects of Chronic and Acute Pulmonary Hyperinflation on Phrenic Nerve Conduction in Patients with COPD.

In patients with moderate-to-severe Chronic Obstructive Pulmonary Disorder (COPD), pulmonary hyperinflation can occur at rest and increase during episodes of exacerbation. Among other mechanical constraints, changes in position and configuration of the diaphragm are also induced by increased end-expiratory lung volume. Both descent and flattening of diaphragm might damage the phrenic nerves by stretching their fibers. The study aimed to investigate the phrenic nerve conduction in COPD patients in stable conditions and during COPD exacerbation. In a group of 11 COPD patients without relevant comorbidities in stable conditions and subsequently in another group of 10 COPD patients during in-hospital COPD exacerbation and recovery, measurements of functional respiratory parameters and assessment of phrenic nerves motor conduction by bilateral electric stimulation were performed concurrently. Significant increase in phrenic nerves latency (p < 0.05), but similar amplitude of motor compound muscle action potential (cMAP) was observed in stable COPD patients vs. matched controls (p < 0.05). However, in COPD patients with resting pulmonary hyperinflation as reliably detected by substantial Inspiratory Capacity reduction (<80% pred.), the mean bilateral latency was longer vs. COPD patients without pulmonary hyperinflation (p < 0.02). During COPD exacerbation, in contrast with mean latency, the mean amplitude of phrenic nerves cMAP improved at discharge when compared with in-hospital admission (p < 0.05). In stable COPD patients the velocity of phrenic nerve conduction was impaired mostly in the presence of pulmonary hyperinflation, while during COPD exacerbation where dynamic pulmonary hyperinflation abruptly occurs, the reversible decrease of cMAP amplitude does suggest a temporary, acute axonal damage of phrenic nerves, potentially contributing to diaphragmatic dysfunction in these circumstances.

Phenotyping-based treatment improves obstructive sleep apnea symptoms and severity: a pilot study.

BACKGROUND: Obstructive sleep apnea is a common disorder characterized by multiple pathogenetic roots. Continuous positive airway pressure (CPAP) is almost always prescribed as the first-line treatment to all patients regardless of the heterogeneous pathophysiology, because it mechanically splints the airways open and reduces the collapsibility of the upper airway. Despite its high efficacy, CPAP is burdened by poor adherence and compliance rates. In this pilot study, we treated OSA patients with composite approaches different than CPAP, tailoring the therapeutic choice on OSA phenotypic traits. METHODS: We used the CPAP dial down technique to assess phenotypic traits in eight OSA patients with BMI<35. According to these traits, patients received personalized therapies for 2-week period, after which we ran a second polygraphy to compare apnea-hypopnea index (AHI) before and after therapy. RESULTS: Two weeks of combined behavioral and pharmacological therapy induced a significant reduction in mean AHI, which dropped from 26 ± 15 at baseline to 9 ± 7 post-treatment (p = 0.01). Furthermore, there was a significant reduction in mean ODI (p = 0.03) and subjective sleepiness (p = 0.01) documented by Epworth Sleepiness Scale (ESS) from baseline to post-treatment recordings. CONCLUSIONS: Treating OSA patients with a personalized combination of pharmacological and behavioral therapies according to phenotypic traits leads to a significant improvement in AHI, ODI, and subjective sleepiness.

Methods for Measuring Lung Volumes: Is There a Better One?

BACKGROUND: Accurate measurement of lung volumes is of paramount importance to establish the presence of ventilatory defects and give insights for diagnostic and/or therapeutic purposes. OBJECTIVES: It was the aim of this study to measure lung volumes in subjects with respiratory disorders and in normal controls by 3 different techniques (plethysmographic, dilutional and radiographic methods), in an attempt to clarify the role of each of them in performing such a task, without any presumptive 'a priori' superiority of one method above others. Patients andMethods: In different groups of subjects with obstructive and restrictive ventilatory defects and in a normal control group, total lung capacity, functional residual capacity (FRC) and residual volume were measured by body plethysmography, multi-breath helium (He) dilution and radiographic CT scan method with spirometric gating. RESULTS: The 3 methods gave comparable results in normal subjects and in patients with a restrictive defect. In patients with an obstructive defect, CT scan and plethysmography showed similar lung volumes, while on average significantly lower lung volumes were obtained with the He dilution technique. Taking into account that the He dilution technique does primarily measure FRC during tidal breathing, our data suggest that in some patients with an obstructive defect, a number of small airways can be functionally closed at end-expiratory lung volume, preventing He to reach the lung regions subserved by these airways. CONCLUSION: In all circumstances, both CT scan with spirometric gating and plethysmographic methods provide similar values of lung volumes. In contrast, the He dilution method can measure lower lung volumes in some patients with chronic airflow obstruction.

Cardiac Sympathetic Hyperactivity in Patients with Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) coexist in 0.5-1% of the general population. Both OSA and COPD are associated with increased sympathetic nervous activity, and patients affected by both disorders have higher risk for increased morbidity and mortality as compared with patients with COPD or OSA alone. We tested the hypothesis that patients with COPD and OSA (Overlap syndrome) have higher sympathetic and lower parasympathetic modulation of heart rate variability (HRV) in comparison with patients suffering from COPD or OSA alone. HRV indices in the frequency domain were evaluated from daytime electrocardiographic recordings in 14 patients with both severe OSA (apnea-hypopnea index ≥ 30) and mild-to-moderate COPD and compared with those with OSA (n = 24) or COPD (n = 16) alone. We found that, in the Overlap syndrome group, high-frequency (HF, 0.4-0.15 Hz) power was significantly lower (0.18 nu vs 0.34 nu in OSA and 0.44 nu in COPD patients, p < 0.01) and low-frequency (LF, 0.15-0.05 Hz) power was significantly greater (0.82 nu vs 0.66 nu in OSA and 0.57 nu in COPD patients, p < 0.01) compared with COPD and OSA groups. Patients with both OSA and COPD had higher LF/HF ratio as compared with patients in OSA and COPD groups (4.5 [5.9] vs 1.9 [2.6] and 1.3 [1.3], respectively, p < 0.01). For the Overlap syndrome group, there was a significant direct relationship between LF/HF ratio and residual volume (r2 = 0.62, p = 0.007). These findings show that patients with both OSA and COPD have higher sympathetic modulation of heart rate compared with those with OSA or COPD alone. Furthermore, the findings provide a potential mechanism for the increased morbidity and mortality reported in patients suffering from both disorders, suggesting new therapeutic perspectives in Overlap syndrome.

Tidal airway closure in asthma and COPD.

Functional closure of small airways can occur during tidal breathing above functional residual capacity (FRC) both in asthma and COPD patients, especially during exacerbations. Such event has several noxious consequences on gas exchange, airway hyperresponsiveness and mechanical stress and strain within lung tissue and airway wall, mostly due to increase in ventilation heterogeneity. The availability of simple functional tests based on sequential measurements of lung volumes (i.e.: FRC), by plethysmography and dilutional techniques may reveal and monitor easily tidal airway closure that can be and should be treated with the aim of abolishing or at least reducing this dangerous condition.

Echocardiographic evaluation in subjects with α1-Antitrypsin deficiency.

BACKGROUND: α1-Antitrypsin (AAT) deficiency (AATD) is a genetic condition associated with early-onset panacinar emphysema and, less often, vascular disease. Recently, abnormal elastic properties of ascending aortic wall were described in ZZ genotype AATD subjects who incidentally showed an increased left ventricular mass. MATERIALS AND METHODS: To evaluate biventricular dimensions, valvular apparatus, systolic and diastolic function, 33 AATD subjects with ZZ genotype and 33 healthy subjects matched for age and sex underwent a complete echocardiographic assessment. RESULTS: Compared to controls, AATD subjects showed increased left ventricular mass (160 ± 59 g vs. 121 ± 70 g, P < 0.001), a higher incidence of left and right ventricular diastolic dysfunction (30% vs. 16%, P < 0.001 and 45% vs. 20%, P < 0.001, respectively) and mitral valve prolapse (35% vs. 6%, P < 0.001). In contrast, there was no difference between the two groups in diameters and systolic function of both ventricles and in the ejection fraction of left ventricle. The functions of aortic and tricuspidal valves were also similar. CONCLUSIONS: In the presence of greater left ventricular mass, a significantly higher incidence of left and right ventricular diastolic dysfunction and mitral valve prolapse occurs in AATD subjects (ZZ genotype). These findings strongly suggest an abnormal remodelling process in cardiac tissue in AATD.

The role of bronchial epithelial cells in the pathogenesis of COPD in Z-alpha-1 antitrypsin deficiency.

BACKGROUND: Alpha-1 antitrypsin is the main inhibitor of neutrophil elastase in the lung. Although it is principally synthesized by hepatocytes, alpha-1 antitrypsin is also secreted by bronchial epithelial cells. Gene mutations can lead to alpha-1 antitrypsin deficiency, with the Z variant being the most clinically relevant due to its propensity to polymerize. The ability of bronchial epithelial cells to produce Z-variant protein and its polymers is unknown. METHODS: Experiments using a conformation-specific antibody were carried out on M- and Z-variant-transfected 16HBE cells and on bronchial biopsies and ex vivo bronchial epithelial cells from Z and M homozygous patients. In addition, the effect of an inflammatory stimulus on Z-variant polymer formation, elicited by Oncostatin M, was investigated. Comparisons of groups were performed using t-test or ANOVA. Non-normally distributed data were assessed by Mann-Whitney U test or the Kruskal-Wallis test, where appropriate. A P value of < 0.05 was considered to be significant. RESULTS: Alpha-1 antitrypsin polymers were found at a higher concentration in the culture medium of ex vivo bronchial epithelial cells from Z-variant homozygotes, compared with M-variant homozygotes (P < 0.01), and detected in the bronchial epithelial cells and submucosa of patient biopsies. Oncostatin M significantly increased the expression of alpha-1 antitrypsin mRNA and protein (P < 0.05), and the presence of Z-variant polymers in ex vivo cells (P < 0.01). CONCLUSIONS: Polymers of Z-alpha-1 antitrypsin form in bronchial epithelial cells, suggesting that these cells may be involved in the pathogenesis of lung emphysema and in bronchial epithelial cell dysfunction.

Evaluation of Clinical Remission in Best-Performing Severe Asthmatic Patients Treated for Three Years with Mepolizumab.

BACKGROUND: In its severe form, where possible, asthma is treated using biological drugs in order to reduce, as much as possible, the use of systemic steroids. Mepolizumab is effective for severe asthma based on key outcomes such as exacerbation and steroid dependence. Its efficacy in terms of the criteria for clinical remission in the short and long term has become of interest. OBJECTIVE: We aimed to evaluate the effect of mepolizumab in the achievement of clinical remission after 3 years of administration. METHODS: In this study, 71 patients who continued mepolizumab for 3 years were assessed for clinical remission according to six different published sets of remission criteria. RESULTS: According to the criteria, 39-52% of patients experienced complete remission in the first year, increasing to 51-73% at 3 years. By classifying patients according to partial and complete remission criteria, proposed by the SANI, we observe 22% of patients in partial remission at one year, achieving complete remission after three years. The baseline factors associated with earlier remission were a higher FEV1, if we consider classifications requiring an FEV1 ≥ 80%, a low OCS dose, and low FeNO levels, in the patients requiring FEV1 stabilization. CONCLUSIONS: Clinical remission is possible for patients treated with mepolizumab. The observations at three years compared with the first year indicated that the factors negatively affecting remission delayed rather than prevented it. Earlier treatment could increase the chances of remission.