COMET: a multicomponent home-based disease-management programme versus routine care in severe COPD.

The COPD Patient Management European Trial (COMET) investigated the efficacy and safety of a home-based COPD disease management intervention for severe COPD patients.The study was an international open-design clinical trial in COPD patients (forced expiratory volume in 1 s <50% of predicted value) randomised 1:1 to the disease management intervention or to the usual management practices at the study centre. The disease management intervention included a self-management programme, home telemonitoring, care coordination and medical management. The primary end-point was the number of unplanned all-cause hospitalisation days in the intention-to-treat (ITT) population. Secondary end-points included acute care hospitalisation days, BODE (body mass index, airflow obstruction, dyspnoea and exercise) index and exacerbations. Safety end-points included adverse events and deaths.For the 157 (disease management) and 162 (usual management) patients eligible for ITT analyses, all-cause hospitalisation days per year (mean±sd) were 17.4±35.4 and 22.6±41.8, respectively (mean difference -5.3, 95% CI -13.7 to -3.1; p=0.16). The disease management group had fewer per-protocol acute care hospitalisation days per year (p=0.047), a lower BODE index (p=0.01) and a lower mortality rate (1.9% versus 14.2%; p<0.001), with no difference in exacerbation frequency. Patient profiles and hospitalisation practices varied substantially across countries.The COMET disease management intervention did not significantly reduce unplanned all-cause hospitalisation days, but reduced acute care hospitalisation days and mortality in severe COPD patients.

Effect of erdosteine on the rate and duration of COPD exacerbations: the RESTORE study.

Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) exacerbations and antioxidants can decrease exacerbation rates, although we lack data about the effect of such drugs on exacerbation duration.The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40-80 years with Global Initiative for Chronic Obstructive Lung Disease stage II/III. Patients received erdosteine 300 mg twice daily or placebo added to usual COPD therapy for 12 months. The primary outcome was the number of acute exacerbations during the study.In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8 years, forced expiratory volume in 1 s 51.8% predicted) erdosteine reduced the exacerbation rate by 19.4% (0.91 versus 1.13 exacerbations·patient-1·year-1 for erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild exacerbations was 57.1% (0.23 versus 0.54 exacerbations·patient-1·year-1 for erdosteine and placebo, respectively; p=0.002). No significant difference was observed in the rate of moderate and severe exacerbations (0.68 versus 0.59 exacerbations·patient-1·year-1 for erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group. Erdosteine decreased the exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63 days for erdosteine and placebo, respectively; p=0.023). Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p<0.001), but did not affect the St George's Respiratory Questionnaire score or the time to first exacerbation.In patients with COPD, erdosteine can reduce both the rate and duration of exacerbations. The percentage of patients with adverse events was similar in both the placebo and erdosteine treatment groups.

Erdosteine reduces the exercise-induced oxidative stress in patients with severe COPD: Results of a placebo-controlled trial.

BACKGROUND: Erdosteine (ER), a multimechanism, mucoactive agent with anti-oxidant and anti-inflammatory properties, has been shown to improve lung function, decrease plasma reactive oxygen species (ROS), and 8-isoprostane levels in patients with chronic obstructive pulmonary disease (COPD). AIM: To assess vs. placebo the effect of ER on the exercise-induced oxidative stress by measuring and comparing the release of pro-inflammatory mediators in severe COPD patients. METHODS: The double blind, placebo controlled study was carried out in 24 severe (GOLD Class III) COPD patients, aged >40 yr, randomized to receive either oral ER (600 mg/day, 8 males, mean age 70.5 yr) or placebo (9 males, mean age 70.8 yr) for 10 days. All patients performed a 6-min walking test (6MWT) before and after both treatments. RESULTS: Mean ROS plasma levels increased significantly, but equally, in each group following the baseline 6MWT (p = ns). At the end of both treatments, a significant difference in mean plasma ROS increase from baseline became clear between the ER (+14.6% ± 2.7) and the placebo group (+24.4% ± 3.8) after the second 6MWT (p < 0.025). A similar significant trend was proved for the mean 8-isoprostane increase, which changed from baseline by +14.1% ± 2.6 in the ER, and by +26.3 ± 2.9 in the placebo group, respectively, after the second 6MWT (p < 0.006). CONCLUSIONS: Data from the present study are suggesting that ER is effective in reducing the release of inflammatory mediators due to the exercise-induced oxidative stress in severe COPD patients.

Patient Heterogeneity in Health Economic Decision Models for Chronic Obstructive Pulmonary Disease: Are Current Models Suitable to Evaluate Personalized Medicine?

OBJECTIVES: To assess how suitable current chronic obstructive pulmonary disease (COPD) cost-effectiveness models are to evaluate personalized treatment options for COPD by exploring the type of heterogeneity included in current models and by validating outcomes for subgroups of patients. METHODS: A consortium of COPD modeling groups completed three tasks. First, they reported all patient characteristics included in the model and provided the level of detail in which the input parameters were specified. Second, groups simulated disease progression, mortality, quality-adjusted life-years (QALYs), and costs for hypothetical subgroups of patients that differed in terms of sex, age, smoking status, and lung function (forced expiratory volume in 1 second [FEV1] % predicted). Finally, model outcomes for exacerbations and mortality for subgroups of patients were validated against published subgroup results of two large COPD trials. RESULTS: Nine COPD modeling groups participated. Most models included sex (seven), age (nine), smoking status (six), and FEV1% predicted (nine), mainly to specify disease progression and mortality. Trial results showed higher exacerbation rates for women (found in one model), higher mortality rates for men (two models), lower mortality for younger patients (four models), and higher exacerbation and mortality rates in patients with severe COPD (four models). CONCLUSIONS: Most currently available COPD cost-effectiveness models are able to evaluate the cost-effectiveness of personalized treatment on the basis of sex, age, smoking, and FEV1% predicted. Treatment in COPD is, however, more likely to be personalized on the basis of clinical parameters. Two models include several clinical patient characteristics and are therefore most suitable to evaluate personalized treatment, although some important clinical parameters are still missing.

Expert opinion on the cough hypersensitivity syndrome in respiratory medicine.

In 2011, a European Respiratory Society Task Force embarked on a process to determine the position and clinical relevance of the cough hypersensitivity syndrome, a disorder characterised by troublesome coughing often triggered by low levels of thermal, mechanical or chemical exposure, in the management of patients with chronic cough. A 21-component questionnaire was developed by an iterative process supported by a literature review. 44 key opinion leaders in respiratory medicine were selected and interviewed as to their opinions. There was a high degree of unanimity in the responses obtained, with all opinion leaders supporting the concept of cough hypersensitivity as a clinically useful paradigm. The classic stratification of cough into asthmatic, rhinitic and reflux-related phenotypes was supported. Significant disparity of opinion was seen in the response to two questions concerning the therapy of chronic cough. First, the role of acid suppression in reflux cough was questioned. Secondly, the opinion leaders were split as to whether a trial of oral steroids was indicated to establish a diagnosis of eosinophilic cough. The cough hypersensitivity syndrome was clearly endorsed by the opinion leaders as a valid and useful concept. They considered that support of patients with chronic cough was inadequate and the Task Force recommends that further work is urgently required in this neglected area.

Usability of inhaler devices: a parameter currently misused.

Inhalation represents the most convenient route for delivering respiratory drugs. Delivery systems showed a huge technological progress and several pocket inhalers had been engineered over the last decades for clinical use. Despite the growing technological efforts aimed to simplify the inhalation procedures and optimize the therapeutic outcomes, the effectiveness of drug inhalation through inhalers still represents a major challenge in respiratory medicine. Patients may actually incur in different types of critical errors when using all inhalers and are not capable to inhale throughout all devices equally well. Therefore, the choice of the most suitable and convenient device to prescribe still is a critical issue in real life. Usability is the only comprehensive parameter consenting the effective and objective assessment of pocket inhalers' performance, and allowing their objective comparison and ranking. Unpredictable discrepancies are in fact easily detectable between inhalers (even belonging to the same class) in terms of Usability, independently of the patient's awareness. The reasons were described and discussed for each class of inhalers presently available. Usability is a multidimensional parameter that is much more multifaceted and complex than usually presumed. Usability takes origin from the integrated, balanced and objective assessment of the role played by several factors from different domains, such as: factors related to patient's beliefs, to patients' behavioural components, to device engineering and to the overall cost. Usability is the key parameter for assessing and optimizing the appropriateness of any inhalation treatment through whatever device. Usability would also represent a key investigational instrument for supporting the future development of -innovative and more performing inhaler devices objectively.

Single-Breath Simultaneous Measurement of DLNO and DLCO as Predictor of the Emphysema Component in COPD - A Retrospective Observational Study.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterized by heterogeneous abnormalities of the airways and lung parenchyma that cause different clinical presentations. The assessment of the prevailing pathogenetic components underlying COPD is not usually pursued in daily practice, also due to technological limitations and cost. Aim: To assess non-invasively the lung emphysema component of COPD by the simultaneous measurement of DLNO and DLCO via a single-breath (sDLNO and sDLCO). Methods: COPD patients aged ≥40 years of both genders were recruited consecutively and labelled by computed tomography as "with significant" emphysema (>10% of CT lung volume) or "with negligible" emphysema otherwise. Current lung function tests such as sDLNO, sDLCO and Vc (the lung capillary blood volume) were measured. All possible subsets of independent spirometric and diffusive parameters were tested as predictors of emphysema, and their predicted power compared to each parameter alone by ROC analysis and area under the curve (AUC). Results: Thirty-one patients with "significant emphysema" were compared to thirty-one with "negligible emphysema". FEV1 and FEV1/FVC seemed to be the best spirometric predictors (AUC 0.80 and 0.81, respectively), while sDLCO and Vc had the highest predicted power among diffusive parameters (AUC 0.92 and 0.94, respectively). sDLCO and Vc values were the parameters most correlated to the extent of CT emphysema. Six subsets of independent predictors were identified and included at least one spirometric and one diffusive parameter. According to goodness-to-fit scores (AIC, BIC, log-likelihood and pseudo R2), RV coupled with sDLCO or Vc proved the best predictors of emphysema. Conclusion: When investigating the parenchymal destructive component due to emphysema occurring in COPD, sDLNO, sDLCO and Vc do enhance the predictive power of current spirometric measures substantially. sDLNO, sDLCO and Vc contribute to phenotype of the main pathogenetic components of COPD easily and with high sensitivity. Organizational problems, radiation exposure, time and costs could be reduced, while personalized and precision medicine could be noticeably implemented.

Sub-Optimal Compliance to Long-Term Inhalation Strategies and Poorer Health Care Outcomes Associated with Extended Tattoos in Adolescents with Mild-to-Moderate Bronchial Asthma.

BACKGROUND: Patients' compliance to inhalation therapy is usually sub-optimal in young asthmatics. Adolescents poorly compliant to regular anti-asthma treatments and those with tattoos (and the associated attitude) can share some personality traits and maladaptive behaviors. This relationship has not been investigated. OBJECTIVE: To assess if "extended" tattoos can predict long-term compliance to regular therapy of adolescents with mild-to-moderate asthma. METHODS: A 12-month retrospective observational investigation was conducted on non-smoker asthmatic adolescents of both genders. Patients assuming <70% of prescribed vilanterol/fluticasone furoate o.d. were defined as "non-compliant". Tattoo surfaces were defined as "mild" or "extended" if they were < or ≥400 cm2, respectively. The relationship between tattoos and compliance on the evolution of resources consumption at 6 and 12 months was assessed by generalized estimating equation (GEE) models at the first and second semester of the treatment period. RESULTS: It was found that 13.2% of compliant adolescents had mild tattoos, while 47.2% of non-compliant adolescents had mild-to-extended tattoos (odds ratio (OR) 6.91, 95% CI 2.49 to 19.17, p < 0.001). The mean annual adherence to treatment was 57.8% ± 10.1 SD expected doses in non-compliant subjects with "mild tattoos" (54.8 cm2 ± 36.9 SD), but 38.6% ± 11.4 SD expected doses in those with "extended tattoos" (568.4 cm2 ± 111.6 SD, p < 0.001). Total cost proved to be a linear trend from the lowest values of compliant patients with no/mild tattoos (EUR 65.22 at 6 months and EUR 33.63 at 12 months) to the highest values of non-compliant adolescents with extended tattoos (EUR 330.75 at 6 months and EUR 297.34 at 12 months). CONCLUSIONS: Tattoo extension might be used as a reliable predictor of poor compliance and higher health care costs in adolescents with mild-to-moderate asthma. Patients characterized by poor compliance to a long-term therapeutic strategy and tattooing attitude likely share some aspects of their personality profile.

mRNA vaccines protect from the lung microvasculature injury and the capillary blood volume loss occurring in SARS-CoV-2 paucisymptomatic infections.

INTRODUCTION: The reduction of lung capillary blood volume (Vc) had been identified as the microvascular injury mostly underlying the respiratory Long-COVID syndrome following post-COVID-19 pneumonia. The same kind of injury have been recently also found in several individuals after milder paucisymptomatic SARS-CoV-2 infections. Though current guidelines strongly recommend vac-cination, studies aimed to investigate the in vivo protection of anti-SARS-CoV-2 vaccines on lung microvascular targets still are missing to our best knowledge. AIM: to assess the protection of mRNA vaccines from the reduction of lung capillary blood volume (Vc) caused by pauci-symptomatic SARS.CoV-2 infections in vaccinated compared to unvaccinated individuals. METHODS: Non-smoking individuals with recent paucisymptomatic SARS-CoV-2 infection were divided into vaccinated and unvaccinated groups. Lung function parameters, including single-breath diffusing capacity and microvascular blood volume, were compared between groups. RESULTS: fifty vaccinated and twenty-five unvaccinated well-matched individuals were studied. Differently than usual lung function parameters, only the single-breath simultaneous assessment of sDLCO, sDLNO/sDLCO ratio and Vc allowed to identify the occurrence of the lung microvascular injury with high sensitivity and specificity (p<0.001). CONCLUSION: mRNA vaccines proved to exert a high protection from the loss of lung capillary blood volume (Vc) induced by SARS.CoV-2 paucisymptomatic infections (p<0.001). The availability of this non-invasive investigational model should be regarded as a very helpful tool for assessing and comparing in vivo the protective effect of mRNA vaccines on the human microvascular structures of the deep lung.

Editorial for "Asthma and Its Impact in Adolescents" Special Issue.

Bronchial asthma is a chronic disease related to the atopic condition in most cases but also to other factors (such as infectious diseases; social, economic, environmental, and occupational conditions; exposure to biological irritants; and/or chemical aggressions) [...].

Trend of Bronchial Hyperresponsiveness to Methacholine as a Cost Predictor of Mild-to-Moderate Asthma: A Twelve-Month Survey in Teenagers.

Bronchial asthma is characterized by variable airflow obstruction, airway inflammation, and bronchial hyperresponsiveness (BHR) to non-specific stimuli. The role of underlying airway inflammation and of related long-lasting BHR has been suboptimally investigated in teenagers with mild-to-moderate asthma, as has the corresponding economic impact over time. The aim of the present study was to calculate the cost of mild-to-moderate atopic asthma in teenagers arising from their degree of persisting BHR over a twelve-month period. METHODS: Patients aged 12-18 years with mild-to-moderate symptoms treated with fluticasone fumarate/vilanterol 92/22 mcg daily were retrospectively followed for 12 months. Usual spirometric parameters, BHR to methacholine (MCh), and resource consumption (visits, hospitalizations, systemic steroids and/or antibiotics courses, school days off) were assessed at recruitment (the index date) and after 6 and 12 months. Adherence to treatment was also calculated. The cost of asthma was calculated based on Italian tariffs and published papers. The trend over time in BHR and the association between response to MCh and total cost were investigated by using regression models adjusted for repeated measures. RESULTS: 106 teenagers (53 males, age 15.9 ± 1.6 years) were investigated. The annual cost of asthma proved significantly related to the BHR trend: every increment of a factor 10 in the response to MCh was associated with a saving of EUR 184.90 (95% CI -305.89 to -63.90). BHR was progressively optimized after 6 and 12 months in relation to the patients' compliance to treatment (≥70% of prescribed inhalation doses). CONCLUSIONS: the usual spirometric parameters are largely insufficient to reflect the effects of underlying persistent inflammation in milder forms of asthma in teenagers. In terms of clinical governance, the periodic assessment of non-specific BHR is the appropriate procedure from this point of view. Non-specific BHR proves a reliable procedure for predicting and monitoring the economic impact of mild-to-moderate asthma in teenagers over time.

Patient-centred assessment of COPD in primary care: experience from a cross-sectional study of health-related quality of life in Europe.

BACKGROUND: Most patients with chronic obstructive pulmonary disease (COPD) in Europe are treated in primary care, but perceptions on what guides primary care physicians (PCPs) in managing patients are lacking. AIMS: To describe factors associated with the assessment by PCPs of COPD severity and those associated with impaired health status, as assessed by patient-reported outcomes. METHODS: This cross-sectional study evaluated health-related quality of life (HRQL) in 2,294 COPD patients from five European countries. The severity of COPD was clinically judged by the PCPs and GOLD stage severity was calculated using spirometry data. RESULTS: PCPs' categories of severity reflected a wider range of HRQL scores (St George's Respiratory Questionnaire (SGRQ) total score: mild 30.3; moderate 41.7; severe 55.0; very severe 66.1) than GOLD severity grading (Stage I 38.2; Stage II 41.1; Stage III 49.9; Stage IV 58.5). Multiple ordinal logistic regression models showed that factors most closely related to PCP-rated COPD severity were Medical Research Council (MRC) dyspnoea grade, forced expiratory volume in 1 second (FEV1) percent predicted, HRQL score (either SGRQ or COPD Assessment Test (CAT)), and previous hospitalisations (model generalised R²=0.45 or 0.44 (SQRQ or CAT in model, respectively); all factors p<0.0001). Factors with the highest association with HRQL scores (SGRQ or CAT) were MRC dyspnoea grade, COPD severity (PCP-rated), sputum production, and number of co-morbidities (model R²=0.46 or 0.37 (SQRQ or CAT in multiple linear regression model, respectively); all factors p<0.0001). CONCLUSIONS: PCPs successfully graded COPD severity clinically and appeared to have greater discriminative power for assessing severity in COPD than FEV1-based staging. Their more holistic approach appeared to reflect the patients' HRQL rating and was consistent across five European countries.

Effects of Adherence to Once-Daily Treatment on Lung Function, Bronchial Hyperreactivity and Health Outcomes in Adolescents with Mild-to-Moderate Asthmoka: A Twelve-Month Survey.

Adolescents with asthma are usually insufficiently adherent to regular inhalation treatments, thus limiting their effectiveness. The aim of this study is to investigate the role of adherence to single-inhaler long-acting LABA/ICS dry-powder combination o.d. in affecting lung function, bronchial hyperreactivity, and health outcomes over a twelve-month survey of a group of non-smoking adolescents with mild to moderate asthma. Methods: Age, gender, BMI and atopy, forced expiratory volume in 1 s (FEV1), maximum mid-expiratory flow (MMEF), and maximum expiratory flow at 25% of lung filling (MEF25) were assessed via a Boolean selection process from the institutional database at recruitment, as well as after 6 and 12 months, together with the incidence of exacerbation, school days that were taken off, GP and specialist visits, and systemic steroid and/or antibiotic courses. Adherence was checked monthly via a direct telephone call. Statistics were calculated with an ANOVA trend analysis, assuming p < 0.05. Results: Two well-matched sample groups of 54 subjects each were obtained. The mean annual adherence to treatment ranged from 48.2% doses ± 10.9 sd to 79.3% doses ± 8.8 sd (p < 0.001), regardless of age and gender. Only adolescents that adhered to the o.d. ICS/LABA inhalation regimen progressively achieved complete control of all lung function parameters (FEV1: 0.001; MMEF: p < 0.002; MEF25 < 0.001; <0.001), minimized their bronchial hyperreactivity (p < 0.001), and optimized all health outcomes (p < 0.001­p < 0.002) over the survey duration. Discussion: A good adherence to treatment is essential for asthma management, particularly in young patients. Factors that are totally independent of the complexity of the therapeutic regimen adopted (namely, only a once-daily inhalation in the present survey) probably represent the major reasons limiting the adolescents' adherence. Cultural, educational, behavioral, and psychological factors are frequently involved, are difficult to control, and can present barriers to adolescents' asthma management. Further studies aiming to deeply understand and possibly remove the reasons for such adolescents' attitudes are needed, in cooperation with actions oriented in this direction by families, educators, and health professionals.

Nebivolol: an effective option against long-lasting dyspnoea following COVID-19 pneumonia - a pivotal double-blind, cross-over controlled study.

Background: Pulmonary microvascular occlusions can aggravate SARS-CoV-2 pneumonia and result in a variable decrease in capillary blood volume (Vc). Dyspnoea may persist for several weeks after hospital discharge in many patients who have "radiologically recovered" from COVID-19 pneumonia. Dyspnoea is frequently "unexplained" in these cases because abnormalities in lung vasculature are understudied. Furthermore, even when they are identified, therapeutic options are still lacking in clinical practice, with nitric oxide (NO) supplementation being used only for severe respiratory failure in the hospital setting. Nebivolol is the only selective ß1 adrenoceptor antagonist capable of inducing nitric oxide-mediated vasodilation by stimulating endothelial NO synthase via ß3 agonism. The purpose of this study was to compare the effect of nebivolol versus placebo in patients who had low Vc and complained of dyspnoea for several weeks after COVID-19 pneumonia. Methods: Patients of both genders, aged ≥18 years, non-smokers, who had a CT scan that revealed no COVID-related parenchymal lesions but still complaining of dyspnoea 12-16 weeks after hospital discharge, were recruited. Spirometrical volumes, blood haemoglobin, SpO2, simultaneous diffusing capacity for carbon monoxide (CO) and NO (DLCO and DLNO, respectively), DLNO/DLCO ratio, Vc and exhaled NO (eNO) were measured together with their dyspnoea score (DS), heart frequency (HF), and blood arterial pressure (BAP). Data were collected before and one week after both placebo (P) and nebivolol (N) (2.5 mg od) double-blind cross-over administered at a two-week interval. Data were statistically compared, and p<0.05 assumed as statistically significant. Results: Eight patients (3 males) were investigated. In baseline, their mean DS was 2.5±0.6 SD, despite the normality of lung volumes. DLCO and DLNO mean values were lower than predicted, while mean DLNO/DLCO ratio was higher. Mean Vc proved substantially reduced. Placebo did not modify any variable (all p=ns) while N improved DLco and Vc significantly (+8.5%, p<0.04 and +17.7%, p<0.003, respectively). eNO also was significantly increased (+17.6%, p<0.002). Only N lowered the dyspnoea score (-76%, p<0.001). Systolic and diastolic BAP were slightly lowered (-7.5%, p<0.02 and -5.1%, p<0.04, respectively), together with HF (-16.8%, p<0.03). Conclusions: The simultaneous assessment of DLNO, DLCO, DLNO/DLCO ratio, and Vc confirmed that long-lasting dyspnoea is related to hidden abnormalities in the lung capillary vasculature. These abnormalities can persist even after the complete resolution of parenchymal lesions regardless of the normality of lung volumes. Nebivolol, but not placebo, improves DS and Vc significantly. The mechanism suggested is the NO-mediated vasodilation via the ß3 adrenoceptor stimulation of endothelial NO synthase. This hypothesis is supported by the substantial increase of eNO only assessed after nebivolol. As the nebivolol tolerability in these post-COVID normotensive patients was very good, the therapeutic use of nebivolol against residual and symptomatic signs of long-COVID can be suggested in out-patients.

Long-lasting dyspnoea in patients otherwise clinically and radiologically recovered from COVID pneumonia: a probe for checking persisting disorders in capillary lung volume as a cause.

Background: During SARS-CoV-2 infection, diffuse alveolar damage and pulmonary microvascular abnormalities are critical events that result in gas exchange disorders of varying severity and duration. The only measure of carbon monoxide (CO) diffusing capacity (DLCO) is unable to distinguish the alveolar from the vascular side of present and residual diffusive abnormalities, and measure of nitric oxide (NO) diffusing capacity (DLNO) is also recommended. Dyspnoea, despite being understudied, persists in a significant proportion of patients for several weeks after hospital discharge. The goal of this study was to look into the underlying cause of long-term dyspnoea in patients who were "clinically and radiologically recovered" from COVID pneumonia by assessing DLCO and DLNO at the same time. Methods: Patients of both genders, aged ≥18 years, who had a CT scan showing complete resolution of COVID-related parenchymal lesions were recruited consecutively. Spirometrical volumes, blood haemoglobin, SpO2, DLCO, DLNO and capillary blood volume (Vc) were measured. Data from patients without dyspnoea (group A) and from patients still claiming dyspnoea after 12-16 weeks from their hospital discharge (group B) were statistically compared. Results: Forty patients were recruited: 19 in group A and 21 in group B. Groups were comparable for their general characteristics and spirometrical volumes, that were in the normal range. Mean values for DLCO, DLNO and Vc were significantly and substantially lower than predicted only in patients of group B (p<0.011; p<0.0036; p<0.02; p<0.001, respectively). The DLNO/ DLCO ratio was higher in group B (p<0.001) and inversely correlated to Vc values (-0.3636). Conclusions: The single-breath, simultaneous measurement of DLCO, DLNO, and Vc demonstrated that problems with blood gas exchange can persist even after parenchymal lesions have healed completely. Regardless of the normality of spirometric volumes, there was a significant reduction in lung capillary blood volume. In these patients, the cause of long-term dyspnoea may be related to hidden abnormalities in the vascular side of diffusive function. In the near future, novel therapeutic approaches against residual and symptomatic signs of long-COVID are possible.

The Effect of Maintenance Treatment with Erdosteine on Exacerbation Treatment and Health Status in Patients with COPD: A Post-Hoc Analysis of the RESTORE Dataset.

Purpose: To explore the effect of erdosteine on COPD exacerbations, health-related quality of life (HRQoL), and subjectively assessed COPD severity. Patients and methods: This post-hoc analysis of the RESTORE study included participants with COPD and spirometrically moderate (GOLD 2; post-bronchodilator forced expiratory volume in 1 second [FEV1] 50‒79% predicted; n = 254), or severe airflow limitation (GOLD 3; post-bronchodilator FEV1 30‒49% predicted; n = 191) who received erdosteine 300 mg twice daily or placebo added to usual maintenance therapy for 12 months. Antibiotic and oral corticosteroid use was determined together with patient-reported HRQoL (St George's Respiratory Questionnaire, SGRQ). Patient and physician subjective COPD severity scores (scale 0‒4) were rated at baseline, 6 and 12 months. Data were analyzed using descriptive statistics for exacerbation severity, COPD severity, and treatment group. Comparisons between treatment groups used Student's t-tests or ANCOVA as appropriate. Results: Among GOLD 2 patients, 43 of 126 erdosteine-treated patients exacerbated (7 moderate-to-severe exacerbations), compared to 62 of 128 placebo-treated patients (14 moderate-to-severe exacerbations). Among those with moderate-to-severe exacerbations, erdosteine-treated patients had a shorter mean duration of corticosteroid treatment (11.4 days vs 13.3 days for placebo, P = 0.043), and fewer patients required antibiotic treatment with/without oral corticosteroids (71.4% vs 85.8% for placebo, P < 0.001). Erdosteine-treated GOLD 2 patients who exacerbated showed significant improvements from baseline in SGRQ total scores and subjective disease severity scores (patient- and physician-rated), compared with placebo-treated patients regardless of exacerbation severity. Among GOLD 3 patients, there were no significant differences between treatment groups on any of these measures. Conclusion: Adding erdosteine to the usual maintenance therapy of COPD patients with moderate airflow limitation reduced the number of exacerbations, the duration of treatment with corticosteroids and the episodes requiring treatment with antibiotics. Additionally, treatment with erdosteine improved HRQoL and patient-reported disease severity.

Changes in total IgE plasma concentration measured at the third month during anti-IgE treatment predict future exacerbation rates in difficult-to-treat atopic asthma: a pilot study.

UNLABELLED: In severe, difficult-to-treat atopic asthma with sensitization to perennial allergens, monoclonal antibodies directed against immunoglobulin E (IgE) are recognized to be clinically effective. Omalizumab, a recombinant monoclonal antibody, selectively binds to the high-affinity C-epsilon 3 site of human IgE and inhibits the inflammatory cascade in response to antigenic stimuli. Currently, no indicator is available for predicting patients' responsiveness to long-term omalizumab treatment. This study aims to assess the relationship between early changes in plasma IgE concentration and major outcome variables over a 12-month course of omalizumab. METHODS: Twenty-three nonsmoking, severe asthmatics (14 females; mean age 47.3 years ± 12.0 SD; mean BMI 25.8 kg/m(2) ± 9.6 SD) sensitized to perennial allergens and unresponsive to high doses of common therapies were evaluated during a 12-month period of omalizumab treatment. Variables included total IgE plasma concentrations, Forced Expiratory Volume 1 second (FEV(1)) symptom complaints (Asthma Control Test (ACT) score), number of emergency visits, hospitalizations, and exacerbations. The Wilcoxon signed-rank test was used to compare changes observed after the 1-year omalizumab treatment versus baseline. Statistical modelization was used to determine possible relationships between changes in outcomes after 12 months and early changes in plasma IgE (after 3 months of treatment). RESULTS: The number of emergency visits, hospitalizations, and exacerbations decreased (p < .004, p < .001, and p < .001, respectively) over the 12-months. In contrast, FEV(1) and ACT score substantially increased (both p < .001); the ACT score reaching maximum after only 3 months. The S model showed the best fit and proved the strict relationship between the increase in IgE after 3 months and the exacerbation rate over the 1-year survey (threshold value of ≥250 IU/ml, p < .001). The improvement in FEV(1) was independent of the increase in IgE. CONCLUSIONS: When confirmed on a larger population, early changes in IgE may be used as a predictor of future responders to omalizumab in terms of exacerbation rate, thus minimizing the economic burden of anti-IgE therapy.

Understanding patients with asthma and COPD: insights from a European study.

AIMS: To understand the needs of people with asthma and COPD, and to identify opportunities for improved care. METHODS: Quantitative questionnaire-based survey performed in five European countries on patients with asthma and COPD. Questionnaires were administered to patients using Computer Assisted Web Interview methodology. RESULTS: 1022 patients with asthma (UK [n=190]; Germany [n=214]; France [n=200]; Italy [n=222]; Spain [n=196]) and 719 patients with COPD (UK [n=153]; Germany [n=147]; France [n=145]; Italy [n=140]; Spain [n=134]) were enrolled in the study. 32% of those with asthma and 67% of those with COPD considered that their condition had a significant effect on their quality of life, and stigma and emotional distress was common. Many expressed concern regarding potential medication side effects or that medicines might lose their effect with time. Major discrepancies between expectations and patient satisfaction with the doctor-patient relationship were observed, including a need to be consulted in the choice of inhalers. Consultations were infrequent, and 75% of respondents sought additional information beyond that received during consultations - commonly from the internet. CONCLUSIONS: Patient satisfaction was high but information needs were not addressed and the emotional burden of disease is underappreciated.

Comparison of Consistency, Feasibility, and Convenience of a Novel Compact System for Assessing Lung Volumes and Carbon Monoxide Diffusing Capacity versus Whole Body Plethysmography.

BACKGROUND: The MiniBox+™ is an innovative technique for assessing lung volumes (LVs) and the diffusing capacity of the lung for carbon monoxide (DLco). Differently from the equipment needed for whole body plethysmography (WBP), the MiniBox+ is a small, transportable instrument, which derives total lung capacity (TLC) during tidal breathing by analyzing gas pressures and airflows immediately preceding and immediately following airway occlusions. AIM: To compare the consistency and the feasibility of LV and DLco measurements between the two instruments in different lung function disorders, and their cost of execution. METHODS: Consecutive patients of both genders with obstructive and restrictive respiratory disorders were randomly recruited. LVs and DLco were measured by a randomized sequence. The failure risk, number of attempts to achieve the first reliable measurement, corresponding time spent, and costs per patient were compared. RESULTS: A total of 134 patients were enrolled: 42 asthmatics (32.1%), and 47 patients with obstructive (35.1%) and 44 with restrictive respiratory disorders (32.8%). The overall failure risk was 19.4% for WBP and 8.2% for the MiniBox+ (risk ratio=0.417, 95% CI 0.242 to 0.72). LVs and DLco values proved equal with both techniques, regardless of the patients' age, sex, schooling level, and initial lung disorder. Number of attempts and total time spent in achieving the first reliable measurement were significantly lower with the MiniBox+. Mean cost per patient was €87.58 with WBP and €75.11 with the MiniBox+, with a mean saving of €12.33 (95% CI 5.93 to 18.73), mainly due to the saving in productivity loss. CONCLUSION: LV and DLco measurements with the MiniBox+ were highly consistent with those obtained with WBP. The MiniBox+ proved easier to use (lower failure risk) and more convenient (lower execution costs) than WBP.

The contribution of patients' lung function to the inspiratory airflow rate achievable through a DPIs' simulator reproducing different intrinsic resistance rates.

BACKGROUND: The performance of DPIs depends on several physiological (patient-dependent) and technological (device-dependent) factors. The inspiratory airflow rate is the only active force generated and operating in the system for inducing the required pressure drop and eliciting the resistance-induced turbulence needed to disaggregate the powder through the device. The present study aimed to investigate in the most prevalent respiratory disorders whether and at what extent the inspiratory airflow rate achievable when inhaling through a DPIs' simulator reproducing different intrinsic resistance regimens (low, mid, and high resistance) is affected by peculiar changes in lung function and/or can be predicted by any specific lung function parameter. METHODS: The inspiratory airflow rate was assessed in randomized order by the In-Check DIAL G16 at low, mid, and high resistance regimens in a sample of consecutive subjects at recruitment. Independent predictors of the probability to achieve the expected inhalation airflow rate were investigated by means of a multivariate logistic regression model, specific to the disease. RESULTS: A total of 114 subjects were recruited (asthmatics n=30; COPD n=50, restrictive patients n=16, and normal subjects n=18). The mean values of the expected inspiratory airflow rate achieved proved significantly different within the groups (p<0.0001), independently of sex and age. In asthmatics and in COPD patients, the mid-resistance regimen proved highly associated with the highest mean values of airflow rates obtained. Low- and high-resistance regimens were significantly less likely to consent to achieve the expected level of inspiratory airflow rate (OR<1 in all comparisons). Restrictive patients performed the lowest airflow rates at the low-resistance regimen (p<0.01). Unlike FEV1, RV in asthmatics (OR=1.008); RV and IRaw in COPD (OR=0.587 and OR=0.901, respectively), and FIF and TLC in restrictive patients (OR=1.041, and OR=0.962, respectively) proved the only sensitive predictors of the inspiratory airflow rate achievable at the different resistive regimens. CONCLUSIONS: The intrinsic resistive regimen of DPIs can play a critical role. The patients' lung function profile also affects the extent of their inhalation airflow rate. Some specific lung function parameters (such as: FIF; RV; IRaw; TLC, but not FEV1) may be regarded as specific predictors in real-life. In order to optimize the DPI choice, further to the device's technology, also the current patients' lung function should be properly investigated and carefully assessed.