Persisting exercise ventilatory inefficiency in subjects recovering from COVID-19. Longitudinal data analysis 34 months post-discharge.

BACKGROUND: SARS-CoV-2 infection has raised concerns about long-term health repercussions. Exercise ventilatory inefficiency (EVin) has emerged as a notable long-term sequela, potentially impacting respiratory and cardiovascular health. This study aims to assess the long-term presence of EVin after 34 months and its association with cardiorespiratory health in post-COVID patients. METHODS: In a longitudinal study on 32 selected post-COVID subjects, we performed two cardiopulmonary exercise tests (CPETs) at 6 months (T0) and 34 months (T1) after hospital discharge. The study sought to explore the long-term persistence of EVin and its correlation with respiratory and cardiovascular responses during exercise. Measurements included also V̇O2peak, end-tidal pressure of CO2 (PETCO2) levels, oxygen uptake efficiency slope (OUES) and other cardiorespiratory parameters, with statistical significance set at p < 0.05. The presence of EVin at both T0 and T1 defines a persisting EVin (pEVin). RESULTS: Out of the cohort, five subjects (16%) have pEVin at 34 months. Subjects with pEVin, compared to those with ventilatory efficiency (Evef) have lower values of PETCO2 throughout exercise, showing hyperventilation. Evef subjects demonstrated selective improvements in DLCO and oxygen pulse, suggesting a recovery in cardiorespiratory function over time. In contrast, those with pEvin did not exhibit these improvements. Notably, significant correlations were found between hyperventilation (measured by PETCO2), oxygen pulse and OUES, indicating the potential prognostic value of OUES and Evin in post-COVID follow-ups. CONCLUSIONS: The study highlights the clinical importance of long-term follow-up for post-COVID patients, as a significant group exhibit persistent EVin, which correlates with altered and potentially unfavorable cardiovascular responses to exercise. These findings advocate for the continued investigation into the long-term health impacts of COVID-19, especially regarding persistent ventilatory inefficiencies and their implications on patient health outcomes.

Bone Mineral Density in Mountain, Road Cyclists and Untrained Controls: Exercise, Diet and Hormones.

Purpose: The aim of the study was to compare bone mineral density (BMD) in the lumbar spine (LSBMD) and the femoral neck (FBMD) in male road cyclists (RC n = 39), mountain cyclists (MC n = 30) and controls (C n = 27) and to determine the factors associated with BMD in the same group of participants. Methods: BMD, fat mass (FM) and fat-free mass (FFM) were measured using DXA. Calcium intake (Cal), exercise energy expenditure (EEE) and energy availability (EA) were assessed using self-reported questionnaires. Samples for circulating hormones were also obtained. VO2max was estimated by a cycloergometric test. Results: After adjustment for body mass, in cyclists LSBMD (RC 0.98 ± 0.12; MC 0.98 ± 0.10 g/cm2) was significantly lower than in C (1.11 ± 0.10; p < .001), while FBMD resulted in no significant difference in cyclists compared to C (p = 0.213). EA (kcal/FFM/day) was different in cyclists and in C (p < .05). In C, EEE and EA were positively associated with LSBMD (R = 0.561, R = 0.656, respectively, p < .01), whereas only EA was associated with FBMD (R = 0.554, p < .05); a positive association between EA and FBMD was found in MC (R = 0.464, p < .05). A negative relationship between VO2max and LSBMD in RC (R = -0.418, p < .05) and a positive one between EEE and LSBMD in MC were found (R = 0.605, p < .001). CaI, free testosterone and cortisol were unrelated to BMD. Conclusion: Both the RC and MC had lower LSBMD than C, whereas no difference was found between the two groups of cyclists. The factors associated with BMD are manifold, vary in relation to the measurement site and are likely different in RC, MC and C.

IL18 Gene Polymorphism Is Associated with Total IgE in Adult Subjects with Asthma.

The allergic asthma phenotype is characterized by a T helper type 2 (Th2) immune response, based on Immunoglobulin E (IgE)-mediated type 1 hypersensitivity reactions. Total IgE is the sum of all IgE types produced by the human body and is used as a biomarker of inflammation in asthma. We analysed data collected in 143 asthma cases (median age 42.1 years) from the general Italian population (GEIRD survey; 2008-2010) to identify single nucleotide polymorphisms (SNPs) in candidate genes that are associated with total IgE in adult subjects with asthma. These patients reported respiratory symptoms in response to perennial allergens and provided data on 166 SNPs tagging 50 candidate genes or gene regions. Replication of the statistically significant results was performed in 842 asthma cases from other European countries (ECRHS II survey; 1998-2002). SNP rs549908 in interleukin 18 (IL18) gene was significantly associated with total IgE in GEIRD, and this result was replicated in ECRHS II. SNP rs1063320 in the human leukocyte antigen G (HLA-G) gene was identified in GEIRD, but this association was not replicated in ECRHS II. Further investigating IL18 and its biological pathways could be important for developing new therapeutic targets, due to its involvement in inflammatory response processes.

Circulating eosinophil levels and lung function decline in stable chronic obstructive pulmonary disease: a retrospective longitudinal study. / Níveis de eosinófilos circulantes e declínio da função pulmonar em doença pulmonar obstrutiva crônica estável: um estudo longitudinal retrospectivo.

OBJECTIVE: Whether blood eosinophils (bEOS) in chronic obstructive pulmonary disease (COPD) are associated with disease progression is a topic of debate. We aimed to evaluate whether the differential white blood cell (WBC) count, symptoms and treatment may predict lung function decline and exacerbations in COPD patients. METHODS: We retrospectively examined stable COPD patients with a minimum follow-up of 3 years at our outpatients' clinic. We collected information about lung volumes (FEV1, FVC), the total and differential WBC count, acute exacerbations of COPD (number in the 12 months before the beginning of the study=AE-COPD-B, and during the follow-up=AE-COPD-F), smoking status and treatment. FEV1 decline and AE-COPD-F were described by using a generalized linear model and a 2-level random intercept negative binomial regression, respectively. The models included eosinophil and neutrophil counts as potential predictors and were adjusted by sex, age, smoking status, AE-COPD-B, treatment with bronchodilators and inhaled corticosteroids (ICS). RESULTS: Sixty-eight patients were considered, 36 bEOS- (<170 cells/µL, the median value) and 32 bEOS+ (≥170 cells/µL). ∆FEV1 was higher in bEOS+ than bEOS- (34.86 mL/yr vs 4.49 mL/yr, p=0.029). After adjusting for potential confounders, the eosinophil count was positively (ß=19.4; CI 95% 2.8, 36.1; p=0.022) and ICS negatively (ß=-57.7; CI 95% -91.5,-23.9; p=0.001) associated with lung function decline. bEOS were not found to be associated with the number of AE-COPD-F. CONCLUSION: In stable COPD patients, a higher level of blood eosinophils (albeit in the normal range) predicts a greater FEV1 decline, while ICS are associated with a slower progression of airflow obstruction.

OBJETIVO: Discute-se se eosinófilos no sangue (EOS) na doença pulmonar obstrutiva crônica (DPOC) são associados à evolução da doença. O objetivo deste estudo foi avaliar se a contagem diferencial de células brancas do sangue (CBS), os sintomas e o tratamento podem prever o declínio da função pulmonar e as exacerbações em pacientes com DPOC. MÉTODOS: Foram retrospectivamente examinados pacientes com DPOC estável submetidos a um monitoramento mínimo de três anos em nossas clínicas ambulatoriais. Coletaram-se informações sobre volumes pulmonares (VEF1 e CVF), contagens total e diferencial de CBS, exacerbações agudas de DPOC (número nos 12 meses anteriores ao início do estudo = EA-DPOC-B; e durante o monitoramento = EA-DPOC-F), status tabagístico e tratamento. Os declínios de VEF1 e EA-DPOC-F foram descritos empregando modelo linear generalizado e regressão binomial negativa com interceptação aleatória de nível 2, respectivamente. Os modelos incluíram contagens de eosinófilo e neutrófilo como potenciais preditores e foram ajustados de acordo com sexo, idade, status tabagístico, EA-DPOC-B, tratamento com broncodilatadores e corticosteroides inalados (CSI). RESULTADOS: 68 pacientes foram considerados, dos quais 36 para EOS- (< 170 células/µL, valor da mediana) e 32 para EOS+ (≥ 170 células/µL). ∆VEF1 foi maior em EOS+ do que em EOS- (34,86 mL/ano vs 4,49 mL/ano, p = 0,029). Após o ajuste em relação aos potenciais confundidores, as contagens de eosinófilos (ß = 19,4; CI 95% 2,8,36,1; p = 0,022) e CSI (ß = -57,7; CI 95% -91,5,-23,9; p = 0,001) foram positivamente e negativamente associadas ao declínio da função pulmonar, respectivamente. Os EOS não foram associados ao número de EA-DPOC-F. CONCLUSÃO: Em pacientes com DPOC estável, o maior nível de EOS (embora em um intervalo regular) prevê um maior declínio de VEF1, enquanto os CSIs são associados a uma evolução mais lenta da obstrução do fluxo aéreo.

The Association of Self-Reported Birthweight with Lung Function and Respiratory Diseases: Results from a Multi-Centre, Multi-Case Control Study in Italy.

Early life conditions are associated with lung function and the development of respiratory and non-respiratory illnesses. The relationship with birthweight (BW), however, is conflicting. We examined associations of self-reported BW with lung function and the development of respiratory and also non-respiratory diseases within the GEIRD (Gene-Environment Interaction in Respiratory Diseases) project, an Italian multi-centre, multi-case control study involving cases of COPD, asthma, allergic rhinitis and controls. Multinomial logistic regression was performed with case/control status as response variable; BW as main determinant; and adjusting for sex, age and smoking status. Of the 2287 participants reporting BW, 6.4% (n = 147) had low BW (<2500 g), and this proportion was greater in women than men (7.8% vs. 5.1%; p = 0.006). Both men and women with low BW were shorter than those with normal BW (mean ± SD: 160.2 ± 5.5 vs. 162.6 ± 6.5 cm in women, p = 0.009; 172.4 ± 6.1 vs. 174.8 ± 7.2 cm in men, p < 0.001). Although FEV1 and FVC were reduced in individuals with low BW, this was explained by associations with sex and height. In multivariable analysis, BW was not associated with respiratory diseases in adulthood. However, those with low BW had a higher risk of self-reported hospitalisation for lung disease before the age of two (10.3% vs. 4.1%; p < 0.001), severe respiratory infection before the age of five (16.9% vs. 8.8%; p = 0.001) and hypertension in adulthood (29.9% vs. 23.7%; p = 0.001); however, they had a lower risk of arrhythmia (2.7% vs. 5.8%; p = 0.027).

Six-minute walk distance in healthy subjects: reference standards from a general population sample.

INTRODUCTION: The 6-min walking distance (6MWD) test is a useful tool to obtain a measure of functional exercise capacity. However, reference equations have been mainly based on selected populations or small samples. The purpose of this study was to determine the reference equations to predict the 6MWD in a large Italian population sample of healthy adults of a wide age range. METHODS: In the frame of the multi case-control population-based study Gene Environment Interaction in Respiratory Diseases (GEIRD), we studied 530 healthy subjects: 287 females ranging 21-76 and 243 males ranging 21-78 years of age. We measured 6MWD, demographic and anthropometric data and collected the reported physical activity. A multiple linear regression model for the 6MWD included age, age2, height, weight and physical activity for both sex equations. The two-way interaction age-height and age-weight and the quadratic terms of weight and height were also tested for inclusion separately in each model. RESULTS: The mean ± SD for 6MWD was 581.4 ± 66.5 m (range 383-800 m) for females and 608.7 ± 80.1 m (range 410-875 m) for males. The reference equations were 6MWD = 8.10*age + 1.61*heightcm-0.99*weightkg + 22.58*active-0.10*age2 + 222.55 for females (R squared = 0.238) and 6MWD = 26.80*age + 8.46*heightcm-0.45*weightkg-2.54*active-0.06*age2-0.13*age*heightcm-890.18 for males (R squared = 0.159), where "active" is 1 when the subject is physically active, 0 otherwise. CONCLUSION: This study is the first to describe the 6MWD in a large population sample of young, middle aged and elderly healthy Caucasian subjects, and to determine reference equations. These findings will help to improve the evaluation of Italian and European patients with diseases influencing their functional capacity.

Natural pollen exposure increases in a dose-dependent way Fraction of exhaled Nitric Oxide (FeNO) levels in patients sensitized to one or more pollen species.

BACKGROUND: Co-exposures and polysensitization to several pollen species are very common in real life practice. However, little information exists on allergic symptoms and airway inflammation related to natural pollen exposure in large general population samples. OBJECTIVE: To assess the combined effect of sensitization and/or exposure to one or more pollen species on Fraction of exhaled Nitric Oxide (FeNO) levels. METHODS: Within Gene Environment Interactions in Respiratory Diseases (GEIRD) multicase-control study, 1070 adults from the general population of Verona, Italy, underwent a clinical evaluation including standardized interview, spirometry, skin prick test to inhalants and FeNO measurement. Pollen exposure was assumed, when the mean pollen concentration in the previous week was above the cutoff established by the Italian Aerobiological Monitoring Network. RESULTS: Subjects sensitized to one or more pollen species were respectively 15.5% and 29.6%. FeNO levels were directly related to the number of both pollen species around and pollen-related sensitizations. Median FeNO levels were directly related to number of pollen species around and pollen sensitization. FeNO levels increased from 15.4 ppb (p. 25-p. 75 = 9.9-21.0) outside the pollen season to 17.5 ppb (11.2-30.5) when there were ≥3 pollen species around. Likewise FeNO levels rose from 14.8 ppb (10.0-22.3) in not sensitized subjects, to 16.7 (10.1-25.0) in monosensitized and further to 20.4 (12.3-40.6) in poly-sensitized. According to multivariable quantile regression, median FeNO was 17.9 ppb higher (p. 25-p. 75 = 12.5-23.3) for subjects sensitized and exposed to more than one pollen species, compared to subjects who were neither sensitized nor exposed. Differences in FEV1/FVC between groups were less pronounced (-2.0%, -4.1 to 0.1). Median FeNO level was 15.1 ppb (p. 25-p. 75 = 10.0-23.2) in subjects without pollen-related symptoms, 17.8 ppb (12.1-40.2) in those with nasal symptoms only, and 22.7 ppb (14.7-43.0) in those with asthma-like symptoms (p < 0.001). CONCLUSION AND CLINICAL RELEVANCE: Airways inflammation, evaluated by FeNO, increases in dose-dependent manner from subjects monosensitized to pollen species to those poly-sensitized, especially when asthma-like symptoms on pollen exposure are also reported. This should be considered by allergists during natural pollen seasons when evaluating both pulmonary function and airways inflammation.

Níveis de eosinófilos circulantes e declínio da função pulmonar em doença pulmonar obstrutiva crônica estável: um estudo longitudinal retrospectivo / Circulating eosinophil levels and lung function decline in stable chronic obstructive pulmonary disease: a retrospective longitudinal study

RESUMO Objetivo Discute-se se eosinófilos no sangue (EOS) na doença pulmonar obstrutiva crônica (DPOC) são associados à evolução da doença. O objetivo deste estudo foi avaliar se a contagem diferencial de células brancas do sangue (CBS), os sintomas e o tratamento podem prever o declínio da função pulmonar e as exacerbações em pacientes com DPOC. Métodos Foram retrospectivamente examinados pacientes com DPOC estável submetidos a um monitoramento mínimo de três anos em nossas clínicas ambulatoriais. Coletaram-se informações sobre volumes pulmonares (VEF1 e CVF), contagens total e diferencial de CBS, exacerbações agudas de DPOC (número nos 12 meses anteriores ao início do estudo = EA-DPOC-B; e durante o monitoramento = EA-DPOC-F), status tabagístico e tratamento. Os declínios de VEF1 e EA-DPOC-F foram descritos empregando modelo linear generalizado e regressão binomial negativa com interceptação aleatória de nível 2, respectivamente. Os modelos incluíram contagens de eosinófilo e neutrófilo como potenciais preditores e foram ajustados de acordo com sexo, idade, status tabagístico, EA-DPOC-B, tratamento com broncodilatadores e corticosteroides inalados (CSI). Resultados 68 pacientes foram considerados, dos quais 36 para EOS- (< 170 células/μL, valor da mediana) e 32 para EOS+ (≥ 170 células/μL). ∆VEF1 foi maior em EOS+ do que em EOS- (34,86 mL/ano vs 4,49 mL/ano, p = 0,029). Após o ajuste em relação aos potenciais confundidores, as contagens de eosinófilos (β = 19,4; CI 95% 2,8,36,1; p = 0,022) e CSI (β = -57,7; CI 95% -91,5,-23,9; p = 0,001) foram positivamente e negativamente associadas ao declínio da função pulmonar, respectivamente. Os EOS não foram associados ao número de EA-DPOC-F. Conclusão Em pacientes com DPOC estável, o maior nível de EOS (embora em um intervalo regular) prevê um maior declínio de VEF1, enquanto os CSIs são associados a uma evolução mais lenta da obstrução do fluxo aéreo.

ABSTRACT Objective Whether blood eosinophils (bEOS) in chronic obstructive pulmonary disease (COPD) are associated with disease progression is a topic of debate. We aimed to evaluate whether the differential white blood cell (WBC) count, symptoms and treatment may predict lung function decline and exacerbations in COPD patients. Methods We retrospectively examined stable COPD patients with a minimum follow-up of 3 years at our outpatients' clinic. We collected information about lung volumes (FEV1, FVC), the total and differential WBC count, acute exacerbations of COPD (number in the 12 months before the beginning of the study=AE-COPD-B, and during the follow-up=AE-COPD-F), smoking status and treatment. FEV1 decline and AE-COPD-F were described by using a generalized linear model and a 2-level random intercept negative binomial regression, respectively. The models included eosinophil and neutrophil counts as potential predictors and were adjusted by sex, age, smoking status, AE-COPD-B, treatment with bronchodilators and inhaled corticosteroids (ICS). Results Sixty-eight patients were considered, 36 bEOS- (<170 cells/μL, the median value) and 32 bEOS+ (≥170 cells/μL). ∆FEV1 was higher in bEOS+ than bEOS- (34.86 mL/yr vs 4.49 mL/yr, p=0.029). After adjusting for potential confounders, the eosinophil count was positively (β=19.4; CI 95% 2.8, 36.1; p=0.022) and ICS negatively (β=-57.7; CI 95% -91.5,-23.9; p=0.001) associated with lung function decline. bEOS were not found to be associated with the number of AE-COPD-F. Conclusion In stable COPD patients, a higher level of blood eosinophils (albeit in the normal range) predicts a greater FEV1 decline, while ICS are associated with a slower progression of airflow obstruction.

Importance of Cardiopulmonary Exercise Testing amongst Subjects Recovering from COVID-19.

The cardiopulmonary exercise test (CPET) provides an objective assessment of ventilatory limitation, related to the exercise minute ventilation (VE) coupled to carbon dioxide output (VCO2) (VE/VCO2); high values of VE/VCO2 slope define an exercise ventilatory inefficiency (EVin). In subjects recovered from hospitalised COVID-19, we explored the methodology of CPET in order to evaluate the presence of cardiopulmonary alterations. Our prospective study (RESPICOVID) has been proposed to evaluate pulmonary damage's clinical impact in post-COVID subjects. In a subgroup of subjects (RESPICOVID2) without baseline confounders, we performed the CPET. According to the VE/VCO2 slope, subjects were divided into having EVin and exercise ventilatory efficiency (EVef). Data concerning general variables, hospitalisation, lung function, and gas-analysis were also collected. The RESPICOVID2 enrolled 28 subjects, of whom 8 (29%) had EVin. As compared to subjects with EVef, subjects with EVin showed a reduction in heart rate (HR) recovery. VE/VCO2 slope was inversely correlated with HR recovery; this correlation was confirmed in a subgroup of older, non-smoking male subjects, regardless of the presence of arterial hypertension. More than one-fourth of subjects recovered from hospitalised COVID-19 have EVin. The relationship between EVin and HR recovery may represent a novel hallmark of post-COVID cardiopulmonary alterations.

Gastritis and gastroesophageal reflux disease are strongly associated with non-allergic nasal disorders.

BACKGROUND: Gastroesophageal reflux disease (GERD) has been reported to be significantly associated with chronic rhinosinusitis, but the strength of the association is still debated. AIMS: To evaluate the strength of the association between gastritis/GERD and non-allergic rhinitis (NAR)/allergic rhinitis (AR)/sinusitis. METHODS: We investigated 2887 subjects aged 20-84 years, who underwent a clinical visit in seven Italian centres (Ancona, Palermo, Pavia, Terni, Sassari, Torino, Verona) within the study on Gene Environment Interactions in Respiratory Diseases, a population-based multicase-control study between 2008 and 2014. Subjects were asked if they had doctor-diagnosed "gastritis or stomach ulcer (confirmed by gastroscopy)" or "gastroesophageal reflux disease, hiatal hernia or esophagitis". The association between NAR/AR/sinusitis and either gastritis or GERD was evaluated through relative risk ratios (RRR) by multinomial logistic regression. RESULTS: The prevalence of gastritis/GERD increased from subjects without nasal disturbances (22.8% = 323/1414) to subjects with AR (25.8% = 152/590) and further to subjects with NAR (36.7% = 69/188) or sinusitis (39.9% = 276/691). When adjusting for centre, sex, age, education level, BMI, smoking habits and alcohol intake, the combination of gastritis and GERD was associated with a four-fold increase in the risk of NAR (RRR = 3.80, 95% CI 2.56-5.62) and sinusitis (RRR = 3.70, 2.62-5.23) with respect to controls, and with a much smaller increase in the risk of AR (RRR = 1.79, 1.37-2.35).. CONCLUSION: The study confirmed the association between gastritis/GERD and nasal disturbances, which is stronger for NAR and sinusitis than for AR.

Effects of Respiratory Disorders on Smoking Cessation and Re-Initiation in an Italian Cohort Study.

The present study aims to prospectively assess the influence of respiratory disorders on smoking cessation and re-initiation. Three population-based Italian cohorts answered a questionnaire on respiratory health and smoking habits during 1998-2001 and after a mean follow-up (SD) of 9.1 (0.8) years. Out of 1874 current smokers and 1166 ex-smokers at baseline, 965 (51.5%) and 735 (63.0%) reported their smoking status at follow-up. From current smokers, 312 had stopped smoking at follow-up, while 86 ex-smokers had resumed smoking. People reporting asthma at baseline were more likely to stop smoking than the other subjects (48.6% vs. 31.7%), while people reporting allergic rhinitis or chronic cough/phlegm had a higher probability to resume smoking (16.7% vs. 10.5% and 20.7% vs. 10.4%, respectively). In the multivariable logistic model, smoking relapse strongly decreased with increasing abstinence duration in people without chronic cough/phlegm (OR for ≥7.5 years vs. <7.5 years = 0.23, 95% CI 0.20-0.27), while no effect was detected in people with chronic cough/phlegm (p for interaction = 0.039). Smoking cessation was enhanced in asthmatic subjects, while people with allergic rhinitis or chronic cough/phlegm were at higher risk to resume smoking. Chronic cough/phlegm blunted the decrease in smoking resumption associated with longer abstinence duration.

Impact of Sex on Circulating Leukocytes Composition in COPD Patients.

PURPOSE: Chronic obstructive pulmonary disease is characterized by chronic inflammatory response both at the lung site and at the systemic level. Abnormalities in circulating leukocytes have been reported to occur in COPD patients and have been often shown to correlate with the decline in lung function. COPD affects men and women at a virtually comparable rate, even though distinct sex specific symptoms, progression and therapeutic implications have been described. Nonetheless, these sex-associated differences have not been analyzed in terms of circulating leukocytes. To assess the impact of sex on the changes of circulating immune cells in COPD patients. PATIENTS AND METHODS: Blood samples were collected from 50 COPD patients (31 males, 19 females) and 63 age and sex-matched controls (35 males, 28 females) enrolled in this pilot study. Complete blood cell count and multi-parametric flow cytometry analysis were performed to characterize the leukocyte populations and subsets. RESULTS: Male COPD patients are distinguished from controls by a significant increase in white blood cell counts, neutrophil total and differential counts, and neutrophil-to-lymphocyte ratio. Conversely, a generalized leukocyte decrease discriminated female COPD patients from the related controls. The impact of sex is further remarked by a decrease in adaptive immune cell subpopulations in males as opposed to a consistent increase of innate immune cell types in females correlating with disease severity. CONCLUSION: These data indicate that the definition of specific changes of circulating leukocytes to be used as reliable biomarkers of the disease severity cannot be accomplished irrespectively of sex.

Systemic Inflammatory Response and Outcomes in Community-Acquired Pneumonia Patients Categorized According to the Smoking Habit or Presence of Chronic Obstructive Pulmonary Disease.

The systemic inflammatory response (SIR) may help to predict clinical progression, treatment failure, and prognosis in community-acquired pneumonia (CAP). Exposure to tobacco smoke may affect the SIR; the role of smoking in CAP has not been consolidated. We evaluated the SIR and outcomes of hospitalized CAP patients stratified by smoking habits and the presence of COPD. This retrospective analysis was conducted at the Hospital Clinic of Barcelona. Baseline, clinical, microbiological, and laboratory variables were collected at admission, using C-reactive protein (CRP) levels as a marker of SIR. The study outcomes were pleural complications, hospital stay, non-invasive and invasive mechanical ventilation (IMV), and intensive care unit (ICU) admission. We also considered the in-hospital and 30-day mortality. Data were grouped by smoking habit (non-, former-, and current-smokers) and the presence of COPD. Current smokers were younger, had fewer comorbidities, and fewer previous pneumonia episodes. CRP levels were higher in current smokers than in other groups. Current smokers had a higher risk of pleural complications independent of CRP levels, the presence of pleuritic pain, and a higher platelet count. Current smokers more often required IMV and ICU admission. Current smokers have a greater inflammatory response and are at increased risk of pleural complications.

Biomarkers of Oxidative Stress and Inflammation in Chronic Airway Diseases.

INTRODUCTION: The global burden of chronic airway diseases represents an important public health concern. The role of oxidative stress and inflammation in the pathogenesis of these diseases is well known. The aim of this study is to evaluate the behavior of both inflammatory and oxidative stress biomarkers in patients with chronic bronchitis, current asthma and past asthma in the frame of a population-based study. METHODS: For this purpose, data collected from the Gene Environment Interactions in Respiratory Diseases (GEIRD) Study, an Italian multicentre, multicase-control study, was evaluated. Cases and controls were identified through a two-stage screening process of individuals aged 20-65 years from the general population. Out of 16,569 subjects selected from the general population in the first stage of the survey, 2259 participated in the clinical evaluation. Oxidative stress biomarkers such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-isoprostane and glutathione and inflammatory biomarkers such as Fractional Exhaled Nitric Oxide (FENO) and white blood cells were evaluated in 1878 subjects. RESULTS: Current asthmatics presented higher levels of FENO (23.05 ppm), leucocytes (6770 n/µL), basophils (30.75 n/µL) and eosinophils (177.80 n/µL), while subjects with chronic bronchitis showed higher levels of GSH (0.29 mg/mL) and lymphocytes (2101.6 n/µL). The multivariable multinomial logistic regression confirmed high levels of leucocytes (RRR = 1.33), basophils (RRR = 1.48), eosinophils (RRR = 2.39), lymphocytes (RRR = 1.26) and FENO (RRR = 1.42) in subjects with current asthma. Subjects with past asthma had a statistically significant higher level of eosinophils (RRR = 1.78) with respect to controls. Subjects with chronic bronchitis were characterized by increased levels of eosinophils (RRR = 2.15), lymphocytes (RRR = 1.58), GSH (RRR = 2.23) and 8-isoprostane (RRR = 1.23). CONCLUSION: In our study, current asthmatics show a greater expression of the inflammatory profile compared to subjects who have had asthma in the past and chronic bronchitis. On the other hand, chronic bronchitis subjects showed a higher rate of expression of oxidative stress biomarkers compared to asthmatic subjects. In particular, inflammatory markers such as circulating inflammatory cells and FENO seem to be more specific for current asthma, while oxidative stress biomarkers such as glutathione and 8-isoprostane appear to be more specific and applicable to patients with chronic bronchitis.

Effect of a tailored home-based exercise program in patients with systemic sclerosis: A randomized controlled trial.

OBJECTIVE: The aim was to evaluate the effect of a home-based exercise program on functional capacity, health-related quality of life (HRQoL), and disability, in patients with systemic sclerosis (SSc). METHODS: A 6-month randomized controlled trial was conducted on SSc patients by comparing a home-based minimally supervised exercise program (exercise on a stationary cycle and strengthening of upper limbs; stretching of the hands) with usual care. At baseline and after 3 and 6 months, the patients underwent: 6 minutes walking test; hand mobility in scleroderma test; maximal exercise test on an ergocycle; strength measures (handgrip, quadriceps, and biceps). HRQoL (short-form 36 [SF-36]) and disability (health assessment questionnaire disability index [HAQ-DI]) were measured at the same time. RESULTS: Forty-four patients participated in the study. Twenty-two were randomly assigned to the intervention group (IG, mean age 63.60 ± 10.40 years) and 22 to the control group (CG, 61.80 ± 14.40 years). At 6 months, the distance walked in 6 minutes increased by 46 m (baseline 486, 95% CI 458-513 m; 6 months 532, 95% CI 504-561 m) in IG, whereas it decreased by 5 m (baseline 464, 95% CI 431-497 m; 6 months 459, 95% CI 427-490 m) in CG with a significantly different temporal trend at the between-groups comparison (P < .001). An improvement was also observed for strength measures (handgrip, P = .003; quadriceps, P < .001; biceps, P < .001), for the SF-36 physical component score (P < .001) and for the HAQ-DI (P = .011). CONCLUSIONS: This study indicates that in SSc patients, a minimally supervised home-based exercise program improves physical performance, quality of life, and disability in comparison with usual care.

Dietary flavonoids and respiratory diseases: a population-based multi-case-control study in Italian adults.

OBJECTIVE: To analyse the associations between chronic respiratory diseases and intakes of total flavonoids and their major subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, polymers and proanthocyanidins). DESIGN: Multi-case-control study. SETTING: The analysis was conducted in the frame of the Genes Environment Interaction in Respiratory Diseases (GEIRD) study. The European Prospective Investigation into Cancer and Nutrition FFQ was used to ascertain dietary intake. Multinomial regression models adjusting for age, sex, centre, BMI, smoking habit, alcohol intake, education, total energy intake, vitamin C intake and total fruit intake were used to examine the associations between dietary exposures and the relative risk ratio (RRR) of being a case. PARTICIPANTS: Individuals (n 990) hierarchically defined as follows: cases with asthma (current, n 159; past, n 78), chronic bronchitis (n 47), rhinitis (allergic rhinitis, n 167; non-allergic rhinitis, n 142) and controls (n 97). RESULTS: An increase of 1 sd in flavanones was associated with a reduced risk of non-allergic rhinitis (adjusted RRR = 0·68, 95 % CI 0·47, 0·97); a similar result was found comparing the highest v. lowest quartile of flavanones intake (adjusted RRR = 0·24, 95 % CI 0·10, 0·59). CONCLUSIONS: Flavonoids contained in fruits and vegetables, especially flavanones, might reduce the risk of non-allergic rhinitis. No associations were found between other flavonoids and the considered outcomes.

Chronic bronchitis without airflow obstruction, asthma and rhinitis are differently associated with cardiovascular risk factors and diseases.

BACKGROUND AND OBJECTIVES: Cardiovascular and respiratory diseases can frequently coexist. Understanding their link may improve disease management. We aimed at assessing the associations of chronic bronchitis (CB), asthma and rhinitis with cardiovascular diseases and risk factors in the general population. METHODS: We used data collected in the Gene Environment Interactions in Respiratory Diseases study, an Italian multicentre, multicase-control study. Among 2463 participants (age 21-86, female 50%) who underwent standardized interviews, skin prick and lung function tests, we identified 254 cases of CB without airflow obstruction, 418 cases of asthma without CB, 959 cases of rhinitis alone, and 832 controls. The associations of respiratory diseases with reported cardiovascular risk factors (lifestyles, hypertension, dyslipidaemia), heart disorders (myocardial infarction, coronary thrombosis, angina, aorta or heart surgery) and intermittent claudication were estimated through relative risk ratios (RRR) by multinomial logistic regression models. RESULTS: Compared to controls, CB cases were more likely to be heavy smokers, alcohol consumers, physically inactive, and to suffer from hypertension or dyslipidaemia; rhinitis cases were less obese but more likely to have hypertension. Asthma was significantly associated with current smoking. After adjusting for cardiovascular risk factors, heart disorders were associated with CB (RRR[95%CI]: 1.58[1.12-2.22]) and rhinitis (1.35[0.98-1.85]) and intermittent claudication was associated with CB (3.43[2.52-4.67]), asthma (1.51[1.04-2.21]) and rhinitis (2.03[1.34-3.07]). CONCLUSIONS: CB, asthma and rhinitis were associated with cardiovascular risk factors and diseases. In particular, CB shared with cardiovascular diseases almost all risk factors and was strongly associated with a higher risk of heart disorders and intermittent claudication.

Vegetable but not animal protein intake is associated to a better physical performance: a study on a general population sample of adults.

BACKGROUND: The research was conducted in the frame of a population-based, case control study, called Genes Environment Interaction in Respiratory Disease. OBJECTIVE: To assess the association between protein intake and physical performance in a general population sample. DESIGN: Researchers investigated the association between the participants' dietary information and their physical performance using the 6-min walking test and the distance walked in metres (6MWD) as main outcome measure. Information on dietary intake was collected using the validated European Investigation into Cancer and Nutrition food frequency questionnaires (FFQs). Then, daily intake of energy and macronutrients was estimated by means of the NAF software (nutritional analysis of FFQ). Linear regression models were used to evaluate the associations between vegetable, animal and total protein intakes and the 6MWD. The models were adjusted for socio-demographic features, total fats and available carbohydrate intakes. RESULTS: The participants were 223 subjects (57% females) aged between 23 and 68 years. Their mean vegetable and animal proteins intake for gram/kg of body weight/day were, respectively, 0.4 and 0.7. After adjusting for all the potential confounders, there was a significant increase of 20.0 (95% CI 0.8; 39.2) m in the distance walked for an increase in 10 g/day of vegetable proteins and non-significant variations of -1.8 (95% CI -9.3; 5.7) m for an increase in 10 g/day of animal proteins and of 0.5 (95% CI -6.8; 7.7) for an increase in 10 g/day of total proteins. DISCUSSION AND CONCLUSIONS: Our result suggests a positive role of vegetable proteins on physical performance. Whether this result is related to the high protein intake itself or may be a consequence of the other properties of plant-based foods deserves further investigation.

Depression is associated with poor control of symptoms in asthma and rhinitis: A population-based study.

BACKGROUND: Although many studies have highlighted the link between asthma/rhinitis and depression, it is still unclear which characteristics of these diseases are associated with the risk of depression. We aimed to explore the relationship between depression and asthma or rhinitis in a representative sample of the Italian general population. METHODS: The data were collected in GEIRD, an Italian multicenter, population-based, multicase-control study. 2227 participants (age 21-86 years, female 50%) underwent standardized interviews, skin prick and lung function tests, and were divided into cases of current asthma (n = 528), rhinitis without asthma (n = 972), and controls (n = 727). Two specific questions from the Patient Health Questionnaire (PHQ-2) were asked to identify symptoms of depressed mood and anhedonia, which were used as a proxy of major depression disorder. RESULTS: The prevalence of depression was 16.7%, 11.9%, and 5.1% in subjects with asthma, rhinitis and controls, respectively. Both in asthma and rhinitis, subjects with depression had worse respiratory-health related quality of life and more frequent disease-related symptoms than their non-depressed counterparts. In asthma, depression was associated with poorer disease control. In rhinitis, depression was significantly associated with a disease-related limitations in daily activities and greater risk of symptom exacerbations and prescriptions of medicines for breathing. Cases of rhinitis with depression were less likely to be atopic. CONCLUSIONS: Our results suggest that rhinitis exacerbations, particularly in non-atopic subjects, and low asthma control are strongly related to the presence of depressed mood in adults from the general population.

Health-related quality of life varies in different respiratory disorders: a multi-case control population based study.

BACKGROUND AND OBJECTIVE: Health-related quality of life (HRQL) in respiratory diseases has been generally investigated in clinical settings, focusing on a single disorder. In this study on a general population sample, we assessed the relationship between HRQL and several respiratory diseases studied simultaneously (COPD, current (CA) and past (PA) asthma, allergic (AR) and non-allergic (NAR) rhinitis and chronic bronchitis (CB). METHODS: Controls (n = 328) and cases of NAR (n = 95), AR (n = 163), CB (n = 48), CA (n = 224), PA (n = 126) and COPD (n = 28) were recruited in the centre of Verona in the frame of the Italian multi-case control GEIRD (Gene Environment Interactions in Respiratory Diseases) study; HRQL was measured through the SF-36 questionnaire. The relationships between HRQL (in terms of Physical (PCS) and Mental Component Scores (MCS)), respiratory diseases, and covariates were evaluated. RESULTS: With respect to controls, the adjusted PCS median score was worse in subjects suffering from current asthma (- 1.7; 95%CI:-2.8;-0.6), CB (- 3.8; 95%CI:-5.7;-1.9), and COPD (- 5.6; 95%CI:-8.1;-3.1). MCS was worse in current asthmatics (- 2.2; 95%CI:-4.1;-0.3), CB (- 5.5; 95%CI:-8.7;-2.2), and COPD cases (- 4.6; 95%CI:-8.8;-0.5) as well. CONCLUSIONS: To our knowledge, this is the first study in the general population that analyzed HRQL performing a simultaneous comparison of HRLQ in several respiratory disorders. We found that subjects suffering from COPD, CA, and CB had the poorest HRQL. Clinicians should carefully consider the possible impact of respiratory disorders as CB and not only that of CA and COPD.