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Background Chronic Obstructive Pulmonary Disease (COPD) encompasses various phenotypes that severely limit the applicability of precision respiratory medicine. The present investigation is aimed to assess the circadian rhythm of symptoms in pre-defined clinical COPD phenotypes and its association with health-related quality of life (HR-QoL), the quality of sleep and the level of depression/anxiety in each clinical phenotype. Methods The STORICO (NCT03105999) Italian observational prospective cohort study enrolled COPD subjects. A clinical diagnosis of either chronic bronchitis (CB), emphysema (EM) or mixed COPD-asthma (MCA) phenotype was made by clinicians at enrollment. Baseline early-morning, day-time and nocturnal symptoms (gathered via the Night-time, Morning and Day-time Symptoms of COPD questionnaire), HR-QoL (via the St. George’s Respiratory Questionnaire), anxiety and depression levels (via the Hospital Anxiety and Depression Scale), quality of sleep (via COPD and Asthma Sleep Impact Scale), physical activity (via the International Physical Activity Questionnaire) as well as lung function were recorded. Results 606 COPD subjects (age 71.4 ± 8.2 years, male 75.1%) were studied. 57.9, 35.5 5.3 and 1.3% of the sample belonged to the CB, EM, MCA and EM + CB phenotypes respectively. The vast majority of subjects reported early-morning and day-time symptoms (79.5 and 79.2% in the CB and 75.8 and 77.7% in the EM groups); the proportion suffering from night-time symptoms was higher in the CB than in the EM group (53.6% vs. 39.5%, p = 0.0016). In both CB and EM, indiscriminately, the presence of symptoms during the 24-h day was associated with poorer HR-QoL, worse quality of sleep and higher levels of anxiety/depression. Conclusions The findings highlight the primary classificatory role of nocturnal symptoms in COPD. Trial registration Trial registration number: NCT03105999, date of registration: 10th April 2017.

Asthma may have an impact on lung function decline but conflicting results are reported in forced expiratory volume in one second (FEV) decline. We aimed to describe the changes in FEV in lifelong non-smoking adult asthmatic outpatients during a 10-year follow-up comparing years 1-5 (1st period) with years 6-10 (2nd period) to assess factors affecting these changes. A total of 100 outpatients performed spirometry every 3 months during a 10-year survey. FEV/Ht slope values of the 2nd period reduced significantly respect to the 1st period (p < 0.0001). FEV slopes of years 1-5 and 6-10 were inversely associated with FEV at enrolment (p = 0.02, p = 0.01, respectively). Reversibility and variability FEV showed a significant effect on the 1st period slopes (p = 0.01 and p < 0.04, respectively). Frequent exacerbators in the 1st year had steeper FEV/Ht slopes in the 1st period (p = 0.01). The number of subjects using higher doses of ICS was significantly lower at the 10th years respect to the 5th and the 1st year (p < 0.001, p = 0.003, respectively). This study shows that FEV decline in treated adult asthmatics non-smokers, over 10-year follow-up, is not constant. In particular, it slows down over time, and is influenced by FEV at enrolment, reversibility, variability FEV and exacerbation score in the 1st year.

Following publication of the original article [1], the authors flagged that the article had been provided with the names of the authors (not including the STORICO study group) in the wrong order: the 'Given Names' and Family Names' were erroneously swapped around. Please see this table for the correct order of the names: (Table Presented) This error has now been corrected in the original article and the corrected author list is detailed in this article.

Background Indoor allergens are risk factors for asthma: Thus, the characterization of indoor air quality is important for studying environment–health relationships in children. In particular, Dermatophagoides pteronyssinus is the dominant allergen for asthma. We cross-sectionally investigated the relationships among respiratory symptoms and function, airway inflammation, allergen sensitization, and indoor allergen concentration. Methods One hundred and thirty-two children aging 10-14 years and living in a Southern Mediterranean area were evaluated by parental questionnaires. Spirometry, exhaled nitric oxide (FeNO), skin prick tests, total, and specific serum IgE analyses were performed along with the evaluation of home dust samples for the content in Der p 1 allergen. Three clusters were created on the basis of the presence/absence of wheeze in the last 12 months (Wh12m) and Der p 1-specific IgE level. Results Cluster 1 (Wh12m+/high Der p 1 IgE) presented higher FeNO and poorer pulmonary function (lower FEV1 and FEF25%-75%), while its symptom score was not different from Cluster 2 (Wh12m+/low Der p 1 IgE). Cluster 3 (Wh12m−/low IgE) showed the lowest FeNO values and pulmonary function similar to Cluster 2. Within Cluster 1, both Der p 1-specific IgE and FeNO were positively correlated with dust Der p 1. Conclusions Similar asthma phenotypes may occur in children despite differences in their atopic state. In atopic children, sensitizing allergens in the indoor environment may increase airway inflammation worsening pulmonary function. Moreover, environmental exposures may contribute to the development of asthma-like symptoms also in the absence of atopic sensitization, thus contributing to asthma overdiagnosis.

Large variations in prevalence of atopy and allergic diseases are reported worldwide in children, but in epidemiological studies the use of skin prick tests (SPT) and spirometry along with questionnaires is not common in the Mediterranean Area. The present work was aimed at evaluating the prevalence of current asthma (CA), rhinoconjunctivitis (RC), and eczema (E), with atopy and respiratory function, and the role of risk factors for allergic respiratory diseases. A total of 2150 Italian schoolchildren were cross-sectionally investigated through respiratory questionnaire, SPT, and spirometry. A proportional Venn diagram quantified the distribution of CA, RC, and E, stratifying for allergic sensitization to show differences in prevalence of allergic diseases among subjects with and without positive SPT. CA prevalence was 4.2%, RC 17.9%, and E 5.3%. CA and RC increased, while E decreased, with respect to previous local studies. Allergic sensitization prevalence (evaluated as positive response to at least one SPT) was 39.2%. A double Venn diagram identified 15 categories. Atopic CA was threefold more frequent than non-atopic CA. Atopic vs non-atopic RC and E were 9.6% vs 10.3% and 2.0% vs 3.3%, respectively. Atopic vs non-atopic RC associated with CA were 1.6% vs 0.5%; the same figures for RC associated with E were 0.8% vs 1.3%. Asymptomatic atopic subjects were 27.0%. Atopy, RC, parental asthma, and environmental risk factors were associated with CA. Atopy and environmental factors were risk factors also for RC. Asthma and traffic exposure were linked to reduced lung function. Respiratory allergic diseases are still increasing and largely concomitant in Italian adolescents. Atopy is more important for CA than RC. Avoiding exposures to measured environmental risk factors would prevent 41% of current asthma and 34% of rhinoconjunctivitis.

The extent to which the sensitization to the German cockroach Blattella germanica (BG) affects onset/presence of rhinoconjunctivitis (RC) in children is unknown.

A causal relationship between earth material and human health, although not always proven, is highly plausible because many chemical elements in rocks and soils are directly inhaled by respiration or transmitted, via air, water and vegetation, into food chain and then to human body. It is well known that metals and metalloids may result essential to biochemical and physiological functions, but it is also well known that health problems may derive from either dietary deficiencies or excesses. Among the techniques employed to assess the exposure of living organisms to metals and metalloids present in the environment, the human biomonitoring has attracted the attention of investigators over the past decades. More specifically, the human biomonitoring is a method for assessing human exposure to chemicals by measuring the searched chemicals or their metabolites in human tissues or specimens, such as blood, plasma, serum, breast milk, urine, teeth and also hairs. However, some of these specimens may not always be the best indicators of element intake because of the homeostatic system of control in the human body. Human hairs seem to be particularly appropriate as they offer several advantages. Hair are stable and their composition does not change over short time period. Furthermore, sampling procedure is very easy, requires no specific professional skills, is painless and non-invasive. The present study deals with the trace elements content of hair samples from the scalp of 136 young students, between 11 and 14 years of age, of female and male gender, resident in the metropolitan area of Palermo (80 samples) and in a small rural town, Altavilla (56 samples), 20 km far from Palermo. The concentrations of 18 elements (Al, As, Ba, Cd, Co, Cr, Cu, Li, Mn, Mo, Ni, Pb, Sb, Se, Sr, U, V, Zn) in hair were determined by ICP-MS. In order to eliminate external contamination, each hair sample was firstly properly washed. The obtained results were in line with the ranges of values published in other studies. The most abundant elements resulted Zn, Cu, Al, Sr, Ba, Pb in Palermo as well as in Altavilla, although with different abundance orders. All the remaining analyzed elements were below 1 ppm. Zn is known to be an essential element recognized in more than 300 enzymes depending on this element for catalytic, structural, and regulatory functions. Cu is considered an indispensable catalytic cofactor in redox chemistry for proteins. Al and Sr are typical geogenic elements; their different abundances in the Palermo and Altavilla samples are related to the different lithological site, carbonate rocks in Palermo and calcarenites-clays at Altavilla. Sr is also strictly related to calcium content in bones. The highest levels of most elements were found in Altavilla samples: this may indicate a possible different exposure due to different lifestyles, as evidenced by Al and Pb. In fact, children living at Altavilla spend more time outdoors than those living in Palermo. The higher Ba concentration in children from Altavilla may be also related to the Ba content of local drinkable water. Significant gender-related differences were found for certain elements. This was the case of Sr and Zn, more abundant in female subjects, and Cr, Li, Pb, Sb and U which were more abundant in males. When the elements are subdivided in essential and not essential, and their ratios with respect to aluminum are compared with those in air particulate matter and road dust, it appears evident that some elements typical of anthropogenic sources (Cd, Pb e Sb) are taken by PM10-2.5, PM2.5 and the finest fractions of road dust. Data concerning subjects exposed and not exposed to passive smoke are also reported. Further, it has been examined the relationship between exposure to passive smoke and concentration of nicotine (and its metabolite cotinine) in hairs. A first result of this work is that the reported data and concentration ranges can be used as guidelines for to evaluate environmental or occupational exposure to these elements.

An increased prevalence of bronchial hyper-responsiveness (BHR) has been demonstrated in children from a general population, and in non-asthmatic adults with allergic rhinitis. Thus, also children with allergic rhinitis are expected to be at higher risk of BHR. We evaluated the prevalence of BHR in a sample of non-asthmatic children with allergic rhinitis by means of the methacholine (Mch) bronchial challenge, and by monitorizing the airway patency using the daily peak expiratory flow variability (PEFv). Fifty-one children (ranged 6-15 years of age) with allergic rhinitis, ascertained by skin prick test to inhalant allergens, underwent a 14-day peak expiratory flow monitoring, and a Mch bronchial provocation challenge. Thirty healthy children matched for age, and sex served as control group. Thirty-one children in the rhinitis group (61%), and six (20%) in the control group were Mch+ (Mch provocative dose causing a 20% fall of forced expiratory volume in 1 s respect to baseline

Identifying asthma comorbidities in children is fundamental for improving disease management. We aimed to investigate the frequency of allergy-related comorbidities in children and adolescents with asthma, and to identify associated risk factors and disease burden. Between September 2015 and December 2018, 508 asthmatic patients (5–17 years) were consecutively enrolled. Parents answered a standardized questionnaire on the history of disease and risk factors. Comorbidities were classified based on the involvement of respiratory and/or extra-respiratory districts: asthma only (A, 13%), asthma with respiratory comorbidities (AR, 37%), asthma with extra-respiratory comorbidities (AER, 10%), and asthma with both respiratory and extra-respiratory comorbidities (ARER, 40%). Multinomial logistic regression showed that membership in the AR group was significantly associated with a maternal history of asthma (OR = 3.08, 95% CI: 1.23–7.72), breastfeeding ≥ three months (OR = 1.92, 1.06–3.46), early mold exposure (OR = 2.39, 1.12–5.11), and current environmental tobacco smoke exposure (OR = 2.06, 1.11–3.83). Membership in the AER group was significantly associated with the female gender (OR = 3.43, 1.54–7.68), breastfeeding ≥ three months (OR = 2.77, 1.23–6.22). ARER was significantly associated with all the aforementioned exposures. Patients with AR reported exacerbations in the last 12 months more frequently (p = 0.009). Several personal and environmental risk factors are associated with comorbidities in asthmatic children and adolescents, possibly worsening the disease burden.

This study aimed at surveying lower secondary schools in southern Italy, in a highly polluted area. A community close to an industrial area and three villages in rural areas was investigated. Indoor temperature, relative humidity (RH), gaseous pollutants (CO 2 and NO 2 ), selected biological pollutants in indoor dust, and the indoor/outdoor mass concentration and elemental composition of PM 2.5 were ascertained. Temperature and RH were within, or close to, the comfort range, while CO 2 frequently exceeded the threshold of 1000ppm, indicating inadequate air exchange rate. In all the classrooms, median NO 2 levels were above the WHO threshold value. Dermatophagoides p. allergen concentration was below the sensitizing threshold, while high endotoxin levels were detected in the classrooms, suggesting schools may produce significant risks of endotoxin exposure. Concentration and solubility of PM 2.5 elements were used to identify the sources of indoor particles. Indoor concentration of most elements was higher than outdoors. Resuspension was responsible for the indoor increase in soil components. For elements from industrial emission (Cd, Co, Ni, Pb, Sb, Tl, V), the indoor concentration depended on penetration from the outside. For these elements, differences in rural vs industrial concentrations were found, suggesting industrial sources may influence indoor air quality nearby schools.

Multimorbidity is known to impair Quality of Life (QoL) in patients in a primary setting. Poor QoL is associated with higher dyspnea perception. How multimorbidity and dyspnea perception are related to QoL needs clarification. The aim of the present study is to evaluate the mediating role of dyspnea perception in the relationship between multimorbidity and QoL in adults with and without airflow obstruction in a primary care setting. Seventeen general practitioners participated in the study: a total of 912 adult patients attending the practitioner’s surgery for a generic consultation completed a preliminary respiratory screening; 566 of them answered a respiratory questionnaire between January and June 2014, and 259 of the latter (148 M, aged 40–88) agreed to go through all the of procedures including spirometry, the IMCA and QoL (SF-36 through Physical Health “PCS” and Mental Health components) questionnaires, evaluation of comorbidities and the mMRC Dyspnea Scale. For screening purpose, a cut-off of FEV1/FVC < 70% was considered a marker of airflow obstruction (AO). Of the sample, 25% showed airflow obstruction (AO). No significant difference in mMRC score regarding the number of comorbidities and the PCS was found between subjects with and without AO. Multimorbidity and PCS were inversely related in subjects with (p < 0.001) and without AO (p < 0.001); mMRC and PCS were inversely related in subjects with (p = 0.001) and without AO (p < 0.001). A mediation analysis showed that the relation between number of comorbidities and PCS was totally mediated by mMRC in subjects with AO and partially in subjects without AO. We conclude that the effect of multimorbidity on PCS is totally mediated by mMRC only in AO. Detecting and monitoring mMRC in a primary care setting may be a useful indicator for evaluating a patient’s global health.

Prenatal smoking exposure and early-life respiratory infections are major determinants of asthma during childhood. We investigate the factors influencing allergic sensitization (AS), asthma, and lung function in children and the balance between individual and environmental characteristics at different life stages. 1714 children aged 7&ndash, 16 years and living in southern Italy were investigated using a parental questionnaire, skin prick tests, and spirometry. We found 41.0% AS prevalence: among children without parental history of asthma, male sex, maternal smoking during pregnancy (MatSmoke), and acute respiratory diseases in the first two years of life (ARD2Y) were significant risk factors for AS. MatSmoke was associated (OR = 1.79) with ARD2Y, and this association was influenced by sex. ARD2Y was, in turn, a significant risk factor (OR = 8.53) for childhood current asthma, along with AS (OR up to 3.03) and rhinoconjuctivitis (OR = 3.59). Forced mid-expiratory flow (FEF25&ndash, 75%) was negatively affected by ARD2Y, with a sex-related effect. Thus, males exposed to MatSmoke had significantly lower FEF25&ndash, 75% than unexposed males. Despite the difficulty of discriminating among the complex interactions underlying the development of allergic respiratory diseases, ARD2Y appears to strongly influence both asthma and lung function during childhood. In turn, ARD2Y is influenced by prenatal exposure to tobacco smoke with a sex-dependent effect.

The interaction between IgE antibodies and allergens is a key event in triggering an allergic reaction. The characterization of this region provides information of paramount importance for diagnosis and therapy. Par j 2 Lipid Transfer Protein is one of the most important allergens in southern Europe and a well-established marker of sensitization in Parietaria pollen allergy. The main aim of this study was to map the IgE binding regions of this allergen and to study the pattern of reactivity of individual Parietaria-allergic patients. By means of gene fragmentation, six overlapping peptides were expressed in Escherichia coli, and their IgE binding activity was evaluated by immunoblotting in a cohort of 79 Parietaria-allergic patients. Our results showed that Pj-allergic patients display a heterogeneous pattern of IgE binding to the different recombinant fragments, and that patients reacted simultaneously against several protein domains spread all the over the molecule, even in fragments which do not contain structural features resembling the native allergen. Our results reveal the presence of a large number of linear and conformational epitopes on the Par j 2 sequence, which probably explains the high allergenic activity of this allergen.

Background Asthma and obesity are important and growing health issues worldwide. Obesity is considered a risk factor for asthma, due to the induction of changes in airway mechanics and altered airway inflammation. Methods We cross-sectionally investigated the effect of increased weight on pulmonary function in a large population sample of healthy children, aged 10–17 yrs living in Palermo, Italy. Explanatory effect of weight on lung function variables were evaluated by multiple linear regression models, taking into account height, gender, and age-class. Results Among the 2,393 subjects, FVC and FEV1 were positively correlated to weight. Multiple regression models showed that the weight beta coefficient for FEV1 was significantly lower with respect to that for FVC (0.005 and 0.009 l/kg, respectively), indicating a different magnitude in explanatory effect of weight on FVC and FEV1. Both FEV1/FVC and FEF25–75%/FVC ratios were negatively correlated to weight, while FEF25–75% was not significantly correlated. Similar results were obtained also when 807 symptomatic subjects were introduced in the model through a sensitivity analysis. Conclusion In healthy children, the disproportionate increase of FEV1 and FVC with weight produces airflow decrease and consequently apparent poorer lung function independently from respiratory disease status.

Purpose Rhinitis and conjunctivitis are common diseases worldwide that are frequently associated. Nevertheless, the risk factors for rhinoconjunctivitis are not well-described and the impact of conjunctivitis on rhinitis and asthma in children remains unknown. This study explored the different risk factors and evaluated the burden of rhinoconjunctivitis among adolescents. Methods This was a cross-sectional study conducted on a random sample of schoolchildren, aged 10-17 years, using skin prick tests and a self-administered questionnaire on respiratory health investigating the impact of rhinitis and rhinoconjunctivitis on daily activities. Results A complete evaluation was obtained for 2,150 children. The prevalence of rhinitis alone was 18.2% and rhinitis associated with conjunctivitis was 20.5%. Rhinoconjunctivitis was more frequently associated with females, a parental history of atopy, domestic exposure to mold/dampness, passive smoke exposure, and reported truck traffic in residential streets. Moreover, rhinoconjunctivitis was associated with a higher level of allergic sensitization. The prevalence of current asthma was 1.7% in subjects without rhinitis or rhinoconjunctivitis, 5.1% in rhinitis and 10.7% in rhinoconjunctivitis. In a logistic model, rhinoconjunctivitis yielded a 2-fold risk for current asthma with respect to rhinitis. Subjects with rhinoconjunctivitis had poorer quality of life (QoL); there was an impact on daily activities in 4.6% of rhinitis and 10.7% of rhinoconjunctivitis. Conclusions Ocular symptoms increase the role of rhinitis as a risk factor for asthma and its impact on daily activities in children.

Background: The role of disability and its association with patient-reported outcomes in the nonsevere forms of chronic obstructive pulmonary disease (COPD) has never been explored. Objectives: The aim of this study was to assess, in a cross-sectional real-life study, the prevalence and degree of disability in moderate COPD patients and to assess its association with health status, illness perception, risk of death and well-being. Methods: Moderate COPD outpatients attending scheduled visits were involved in a quantitative research program using a questionnaire-based data collection method. Results: Out of 694 patients, 17.4% were classified as disabled and 47.6% reported the loss of at least one relevant function of daily living. Disabled patients did not differ from nondisabled patients in terms of working status (p = 0.06), smoking habits (p = 0.134) and ongoing treatment (p = 0.823); however, the former showed a significantly higher disease burden as measured by illness perception, health status and well-being. The stepwise regression analysis showed that the modified Medical Research Council (mMRC) score was the most relevant factor related to COPD disability (F = 38.248; p = 0.001). Patient stratification was possible according to the forced expiratory volume in 1 s (FEV1) value and an mMRC score ≥2, which identified disabled patients, whereas the mMRC values were differently associated with the risk of disability. Conclusion: A significant proportion of individuals with moderate COPD reported a limitation of daily life functions, with dyspnea being the most relevant factor inducing disability. Adding the evaluation of patient-reported outcomes to lung function assessment could facilitate the identification of disabled patients.

Background Respiratory allergic symptoms impact on social life and school activities, influencing the patient's mood states. We evaluated the relationships between allergic respiratory diseases and depressive/anxious mood in a large sample of Italian middle school students, using the partial directed acyclic graph (P-DAG). Methods We studied 1283 subjects aged 10–13. A health respiratory questionnaire including questions relevant to socioeconomic status (HCI) and a test for depression and anxiety were administered. All subjects performed spirometry and skin prick tests. Results A causal role of rhinitis on depression was found: the likelihood of being depressed increased from 11.2 to 17.7%, when rhinitis was present. Moreover, a direct effect of low HCI on depressive mood was shown (p