The first, holistic immunological model of COVID-19: Implications for prevention, diagnosis, and public health measures.

The natural history of COVID-19 caused by SARS-CoV-2 is extremely variable, ranging from asymptomatic or mild infection, mainly in children, to multi-organ failure, eventually fatal, mainly in the eldest. We propose here the first model explaining how the outcome of first, crucial 10-15 days after infection, depends on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, mannose-binding lectin). If SARS-CoV-2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high-affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm), leading to complications often requiring intensive therapy and being, in some patients, fatal. Low-moderate physical activity can still be recommended. However, extreme physical activity and oral breathing with hyperventilation during the incubation days and early stages of COVID-19 facilitates re-inhalation and early direct penetration of high numbers of own virus particles in the lower airways and the alveoli, without impacting on the airway's mucosae covered by neutralizing antibodies ("viral auto-inhalation" phenomenon). This allows the virus to bypass the efficient immune barrier of the upper airway mucosa in already infected, young, and otherwise healthy athletes. In conclusion, whether the virus or the adaptive immune response reaches the lungs first is a crucial factor deciding the fate of the patient. This "quantitative and time-/sequence-dependent" model has several implications for prevention, diagnosis, and therapy of COVID-19 at all ages.

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.

Erdosteine: Drug exhibiting polypharmacy for the treatment of respiratory diseases.

Mucoactive drugs are commonly used in the treatment of acute respiratory tract diseases, such as lower and acute respiratory infection and chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD) in which an increased mucus secretion is one of main clinical features. Indeed these drugs are designed to promote secretion clearance and to specifically alter the viscoelastic properties of mucus, restoring an effective mucociliary clearance and reducing broncho-obstructive symptoms. In association with mucolytics, these patients frequently also receive antibiotics to reduce the bacterial load, thus decreasing the release of infectious and pro-inflammatory products. Erdosteine is one of the most used mucoactive agents for the treatment of several respiratory diseases where the overlap of bacterial infection is frequent. Although the effectiveness in the reducing mucus in acute and chronic respiratory disease has been demonstrated for others mucolytic, some of them when given in combination with an antibiotic therapy, could reduce the antibiotic efficacy in some situation. Differently, erdosteine potentiates the antibiotic effect when given in combination with antibiotics. We have reviewed the literature available on both clinical and in vitro studies that have investigated this effect of erdosteine on the effect of antibiotics when used as combined therapy.

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.

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.

Novel study design to assess the utility of the copd assessment test in a primary care setting.

The quality of a consultation provided by a physician can have a profound impact on the quality of care and patient engagement in treatment decisions. When the COPD Assessment Test (CAT) was developed, one of its aims was to aid the communication between physician and patient about the impact of COPD. We developed a novel study design to assess this in a primary care consultation. Primary care physicians across five countries in Europe conducted videoed consultations with six standardised COPD patients (played by trained actors) which had patient-specific issues that the physician needed to identify through questioning. Half the physicians saw the patients with the completed CAT, and half without. Independent assessors scored the physicians on their ability to identify and address the patient-specific issues, review standard COPD aspects, their understanding of the case and their overall performance. This novel study design presented many challenges which needed to be addressed to achieve an acceptable level of robustness to assess the utility of the CAT. This paper discusses these challenges and the measures adopted to eliminate or minimise their impact on the study results.

Utility of COPD Assessment Test (CAT) in primary care consultations: a randomised controlled trial.

BACKGROUND: One of the aims of the COPD Assessment Test (CAT) is to aid communication between the physician and patient about the burden of chronic obstructive pulmonary disease (COPD) on the patient's life. AIMS: To investigate the impact of the CAT on the quality of primary care consultations in COPD patients. METHODS: Primary care physicians across Europe conducted six consultations with standardised COPD patients (played by trained actors). Physicians were randomised to see the patient with the completed CAT (CAT+ arm) or without (no CAT arm) during the consultation. These were videoed and independent assessors scored the physicians on their ability to identify and address patient-specific issues such as depression (sub-score A); review standard COPD issues such as breathlessness (sub-score B); their understanding of the case (understanding score); and their overall performance. The primary endpoint was the global score (sub-scores A+B; scale range 0-40). RESULTS: A total of 165 physicians enrolled in the study and carried out six consultations each; 882 consultations were deemed suitable for analysis. No difference was seen between the arms in the global score (no CAT arm 20.3; CAT+ arm 20.7; 95% CI -1.0 to 1.8; p=0.606) or on sub-score A (p=0.255). A statistically significant difference, though of limited clinical relevance, was observed in mean sub-score B (no CAT arm 8.8; CAT+ arm 9.6; 95% CI 0.0 to 1.6; p=0.045). There was no difference in understanding score (p=0.824) or overall performance (p=0.655). CONCLUSIONS: The CAT is a disease-specific instrument that aids physician assessment of COPD. It does not appear to improve detection of non-COPD symptoms and co-morbidities.

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) [...].

The Extra Cost Due to Non-Adherence to Inhaled Treatments in Adolescents with Mild-to-Moderate Persistent Asthma.

Bronchial asthma has a high socio-economic impact in Western countries. Low adherence to prescribed inhalation treatments contributes to poor asthma control and the higher utilization of healthcare resources. Although adolescents usually do not comply with long-term inhaled treatments prescribed on a regular basis, the related economic consequences still are poorly investigated in Italy. AIM: A 12-month estimation of the economic impact of non-adherence to inhalation treatments in adolescents with mild-to-moderate atopic asthma. METHODS: Non-smoking adolescents aged 12-19 years, without any significant comorbidity, prescribed with inhaled cortico-steroids (ICS) or ICS/long-acting beta(2)-adrenergics (LABA) via dry powder inhalers (DPIs) on a regular basis were automatically selected from the institutional database. Spirometric lung function, clinical outcomes, and pharmacological information were collected. The adolescents' adherence to their prescribed regimen was calculated monthly. Adolescents were divided in two sub-groups based on their adherence to prescriptions: ≤70% (not adherent) or >70% (adherent), and statistically compared (Wilcoxon test, assuming p < 0.05). RESULTS: Overall, 155 adolescents fulfilled the inclusion criteria (males, 49.0%; mean age, 15.6 years ± 2.9 SD; mean BMI, 19.1 ± 1.3 SD). Mean values of lung function were: FEV1 = 84.9% pred. ± 14.8 SD, FEV1/FVC = 87.9 ± 12.5 SD; MMEF = 74.8% pred. ± 15.1 SD and V25 = 68.4% pred. ± 14.9 SD. ICS had been prescribed in 57.4% of subjects and ICS/LABA in 42.6%. Mean adherence to original prescriptions was 46.6% ± 9.2 SD in non-adherent and 80.3% ± 6.6 SD in adherent adolescents, respectively (p < 0.001). The mean rates of hospitalizations, exacerbations, and GP visits; the average duration of absenteeism; the frequency of systemic steroids and antibiotics courses needed over the study period were significantly and substantially lower in adolescents adherent to prescriptions (all p < 0.001). The mean total annual extra cost calculated in the two sub-groups was EUR 705.8 ± 420.9 SD in non-adherent adolescents and EUR 192.1 ± 68.1 SD in adherent adolescents, respectively (p < 0.001), which was 3.7 times higher than in non-adherent adolescents. CONCLUSIONS: In adolescents, the clinical control of mild-to-moderate atopic asthma is directly and strictly related to the degree of adherence to prescribed inhalation therapies. All clinical and economic outcomes prove dramatically poor when adherence is low, and treatable asthma can be frequently mistaken for refractory asthma in these cases. Adolescents' non-adherence impacts the burden of the disease quite substantially. Much more effective strategies centered specifically on adolescents' asthma are needed.

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.

A 36-month study on the cost/utility of add-on omalizumab in persistent difficult-to-treat atopic asthma in Italy.

OBJECTIVE: Omalizumab is a biological treatment for difficult-to-treat allergic asthma. Its mechanism of action relies on impeding the binding of immunoglobulin E (IgE) to specific cellular receptors, thus blocking the inflammatory cascade. At present, no long-term data are available on its cost/effectiveness. The aim of this study is to assess long-term clinical outcomes and to measure the cost/utility of long-term omalizumab use in difficult-to-treat allergic asthmatics. METHODS: The clinical, economic, and quality-of-life (QoL) outcomes of 36-month add-on omalizumab therapy were compared to equivalent outcomes for the year before the therapy's introduction in a cohort (n = 16) of adults with severe uncontrolled atopic asthma on chronic high-dose antiasthma treatments. The variables considered were lung function, IgE levels, health status, Asthma Control Test (ACT) score, QoL (St. George Questionnaire), general practitioner (GP) and specialist visits, number and duration of hospitalizations, emergency room admission, and pharmacological treatment (both dose and duration). Derived calculated indicators were changes in health-related QoL, total healthcare costs, and incremental cost/utility. Data from the two periods were tested for statistically significant differences according to Student's t test and p < .05 was accepted. RESULTS: Add-on omalizumab significantly and progressively improved asthma control and patient health-related QoL. Symptomatic drug and hospital care costs for these patients dropped significantly. A €450 increase in overall monthly costs was observed; however, when health benefits were considered, this cost increase translated into an incremental cost/utility ratio of €23,880 per quality-adjusted life year gained, which is quite a favorable and convenient figure in terms of the willingness to pay for health benefits in industrialized countries. CONCLUSIONS: The 36-month add-on omalizumab therapy persistently improved all clinical outcomes in difficult-to-treat asthmatic patients. Costs were also optimized and related to the extent of long-term health benefits achieved.

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.

Coughing Can Be Modulated by the Hydration Status in Adolescents with Asthma.

A lower thirst sensitivity frequently characterizes children and adolescents. The daily water intake can be frequently insufficient for the homeostasis and the integrity of their airway epithelium. Little is known about the real-life relationship between dehydration and coughing in young students with asthma. The aim was to investigate the effect of dehydration on coughing in asthmatic students aged ≤16 years. A validated questionnaire aimed to investigate their respiratory history and cough incidence was used. Urine samples were also collected for assessing osmolality. Wilcoxon test, the Pearson Chi Square and the Fisher Exact Test were used; p < 0.05 was assumed as significant. Valid data were obtained from 305 healthy and 56 asthmatic students. Mean urine osmolality was significantly higher in asthmatic than in healthy students (1012 ± 197.7 vs. 863.0 ± 223.0 mOsm/kg, respectively; p < 0.001), particularly in symptomatic asthmatic students (1025 ± 191.6 mOsm/kg, p < 0.01). Both the incidence and duration of coughing episodes were directly related to the degree of urine osmolality (both p < 0.001). Dehydration affects the prevalence and the duration of a cough in asthmatic students aged ≤16 years. Adequate daily water intake should be stimulated in these subjects in order to contain their basic cough attitude.

The Emotional Response to Pandemic of Middle- and High-School Students of an Italian Northern Province: The ERP Study.

The COVID-19 outbreak variably affected people's mental reactions worldwide but was only episodically investigated in healthy Italian teenagers. Our aim was to investigate the emotional responses of Italian middle and high school students to the pandemic. An anonymous 10-item questionnaire was distributed in pre-selected school samples. Responders had to score their perceived extent for each reaction from 0 (lowest perception) to 10 (highest perception). A group of adults was selected as control. Generalized linear models were used to estimate differences among adults and students, high school (HS) and middle school (MS) students, and urban (U) and rural (R) MS students. Comparisons were presented as mean difference (Δ) with a 95% confidence interval (CI). A total of 1512 questionnaires (635 adults, 744 HS, 67 UMS, and 66 RMS) were analyzed. Students appeared more indifferent (Δ = 1.97, 1.52-2.41), anxious (Δ = 0.56, 0.07-1.04), aggressive (Δ = 2.21, 1.72-2.70), and depressed (Δ = 1.87, 1.40-2.34) than adults did, and claimed a higher loss of interest in their activities (Δ = 1.21, 0.72-1.70). Students were less disbelieving (Δ = -0.93, -1.50-0.35) and feared for their loved ones (Δ = -0.89, -1.40-0.39). MS students were less affected by the outbreak than HS students were. Furthermore, R-MS students were significantly less aggressive and depressed, but more indifferent and disbelieving than U-MS. Female sex was an independent factor associated to almost all the questionnaire domains. The pattern of the psychological responses to the pandemic in Italian students proved multifaceted. In addition to anxiety, loss of interest in activities, and depression, aggressiveness emerged as the most characterizing mental attitude in response to the pandemic.

Lung Function Can Predict the Expected Inspiratory Airflow Rate through Dry Powder Inhalers in Asthmatic Adolescents.

Several factors affect drug delivery from dry powder inhalers (DPIs). Some are related to patient's physiological characteristics, while others depend on DPIs' technical aspects. The patient's inspiratory airflow rate (IAR) affects the pressure drop and the turbulence needed to disaggregate the powder inside a DPI. The present study investigated whether lung function limitations occurring in asthmatic adolescents affect their IAR when inhaling through a DPI simulator. Eighteen consecutive adolescents with asthma were recruited, and IAR was randomly assessed at low-, mid-, and high-resistance regimens. A multiple logistic model was developed to evaluate the association of patients' lung function characteristics and devices' resistance with the probability to achieve the expected IAR (E-IAR). The mean value of E-IAR achieved seemed to be sex- and age-independent. Low- and high-resistance regimens were less likely to consent the E-IAR level (odds ratio [OR] = 0.035 and OR = 0.004, respectively). Only the basal residual volume and the inspiratory resistance, but not the Forced Expiratory Volume in 1 s (FEV1), seemed to affect the extent of IAR in asthmatic adolescents (OR = 1.131 and OR = 0.290, respectively). The results suggest that the assessment of current lung function is crucial for choosing the proper DPI for asthmatic adolescents.

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.