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Introduction: In the new GOLD classification the reduction of FEV1, expressed as percentage of predicted value (FEV1PP), is considered an important prognostic factor. However, the use of FEV1PP may introduce bias, especially if based on equations derived from populations different from the one under study. We evaluated how well the GOLD classification stratifies the mortality risk when FEV1PP is based on an equation developed in the same population that gave rise to cases, externally developed equations, or as FEV1 divided by cubed height (FEV1/Ht3). Methods: We studied 882 participants aged ≥65 years. Bronchial obstruction was defined using a fixed cut-off of 0.7 for FEV1/FVC. Predicted values of FEV1 were derived from equations based on the same sample of the cases included in this study and from the European Respiratory Society equations. Severity of bronchial obstruction was also classified according to quartiles of FEV1/Ht3. Results: All the classification systems showed a non-statistically significant linear tendency with 5-years mortality risk. For the 15-years mortality, the linear trend across severity stages is more evident for GOLD classifications, with significant increments in the hazard ratio. Stratification by FEV1/Ht3 could better discriminate the functional status of participants. Conclusion: The severity of bronchial obstruction according to GOLD classes may stratify mortality risk better than quartiles of FEV1/Ht3, whereas the second seems to be more suited to stratify the risk of clinical outcomes. Concerns about the use of externally developed reference values to calculate FEV1PP do not seem confirmed, at least for GOLD classification
Introducción: En la nueva clasificación GOLD, la reducción del FEV1 expresada como porcentaje del valor predicho (FEV1PP) se considera un factor pronóstico importante. Sin embargo, usar el FEV1PP puede introducir sesgos, especialmente si se basa en ecuaciones derivadas de poblaciones diferentes de la que se estudia. Se ha evaluado cómo de adecuadamente estratifica GOLD el riesgo de mortalidad cuando el FEV1PP se basa en una ecuación desarrollada con la misma población en la que se dieron los casos, usando ecuaciones desarrolladas externamente, o con el FEV1 dividido por la altura al cubo (FEV1/A3). Métodos: Estudiamos a 882 participantes de edad ≥ 65 años. La obstrucción bronquial se definió utilizando un punto de corte fijo de 0,7 para FEV1/FVC. Los valores pronosticados de FEV1 se derivaron de ecuaciones basadas en la misma muestra de los casos incluidos en este estudio y de las ecuaciones de la European Respiratory Society. La gravedad de la obstrucción bronquial también se clasificó de acuerdo con los cuartiles de FEV1/A3. Resultados: Todos los sistemas de clasificación mostraron una tendencia lineal estadísticamente no significativa en el riesgo de mortalidad a 5 años. Para la mortalidad a 15 años, la tendencia lineal a través de los diferentes estadios de gravedad es más evidente para los estadios GOLD, con incrementos significativos en la razón de riesgo. La estratificación por FEV1/A3 podría discriminar mejor el estado funcional de los participantes. Conclusión: La gravedad de la obstrucción bronquial según la estadificación GOLD puede estratificar mejor el riesgo de mortalidad que los cuartiles de FEV1/A3. Sin embargo, lo segundo parece el método más adecuado para estratificar el riesgo de resultados clínicos. Las reticencias respecto al uso de valores de referencia desarrollados externamente para calcular FEV1PP no parecen confirmarse, al menos para la clasificación GOLD
Assuntos
Humanos , Masculino , Idoso , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Testes de Função Respiratória/métodos , Volume Expiratório Forçado , Obstrução das Vias Respiratórias/complicações , Obstrução das Vias Respiratórias/diagnóstico , Doença Pulmonar Obstrutiva Crônica/classificação , Doença Pulmonar Obstrutiva Crônica/mortalidadeRESUMO
INTRODUCTION: In the new GOLD classification the reduction of FEV1, expressed as percentage of predicted value (FEV1PP), is considered an important prognostic factor. However, the use of FEV1PP may introduce bias, especially if based on equations derived from populations different from the one under study. We evaluated how well the GOLD classification stratifies the mortality risk when FEV1PP is based on an equation developed in the same population that gave rise to cases, externally developed equations, or as FEV1 divided by cubed height (FEV1/Ht3). METHODS: We studied 882 participants aged ≥65 years. Bronchial obstruction was defined using a fixed cut-off of 0.7 for FEV1/FVC. Predicted values of FEV1 were derived from equations based on the same sample of the cases included in this study and from the European Respiratory Society equations. Severity of bronchial obstruction was also classified according to quartiles of FEV1/Ht3. RESULTS: All the classification systems showed a non-statistically significant linear tendency with 5-years mortality risk. For the 15-years mortality, the linear trend across severity stages is more evident for GOLD classifications, with significant increments in the hazard ratio. Stratification by FEV1/Ht3 could better discriminate the functional status of participants. CONCLUSION: The severity of bronchial obstruction according to GOLD classes may stratify mortality risk better than quartiles of FEV1/Ht3, whereas the second seems to be more suited to stratify the risk of clinical outcomes. Concerns about the use of externally developed reference values to calculate FEV1PP do not seem confirmed, at least for GOLD classification.
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BACKGROUND: Whether a fixed cutoff or the lower limit of normal of the FEV1/FVC ratio should be used to diagnose bronchial obstruction is still a matter of debate. This issue is particularly important for elderly people. OBJECTIVES: We used equations applicable up to 90 years of age to evaluate the mortality of elderly people diagnosed with bronchial obstruction using either a fixed cutoff of 0.7 or the lower limit of normal (LLN). METHODS: Participants in the SaRA (Salute Respiratoria nell'Anziano, Italian for "Respiratory Health in the Elderly") study were grouped as follows: FEV1/FVC ≥0.7 and ≥ LLN (n = 535: F-/L-), FEV1/FVC <0.7 but ≥ LLN (n = 118: F+/L-), and FEV1/FVC <0.7 and < LLN (n = 229: F+/L+). We estimated the mortality risk in the three groups over 15 years of follow-up. RESULTS: The mean age was 73 years (58% men). The hazard ratio (HR) for mortality was 1.427 (95% CI: 1.09-1.868) in the F+/L- group and 2.143 (95% CI: 1.13-1.995) in the F+/L+ group. After adjustment for potential confounders, we found no increased mortality in the F+/L- group (HR: 1.007, 95% CI: 0.755-1.342), while the HR in the F+/L+ group was still sizeable (1.474, 95% CI: 1.136-1.911). CONCLUSIONS: As expected, using a fixed cutoff translates in a larger number of people to be classified as having bronchial obstruction. In our sample the increased mortality in the F+/L- group is due to the confounding effect of age and sex. Our study lends support to the use of LLN in elderly people.
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Volume Expiratório Forçado , Pneumopatias Obstrutivas/diagnóstico , Capacidade Vital , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Humanos , Itália/epidemiologia , Pneumopatias Obstrutivas/mortalidade , Masculino , Medição de RiscoRESUMO
BACKGROUND: The forced expiratory volume in the first second (FEV1) is commonly expressed as percentage of its value predicted by equations. The most commonly used equations are poorly applicable to elderly people. Recently, a set of equations (Global Lung Initiative, GLI) has been released that is expected to be more appropriate in this population. OBJECTIVES: We evaluated the agreement of the GLI, European Respiratory Society (ERS), and National Health and Nutrition Examination Survey (NHANES) equations for prediction of FEV1 and compared their discriminative capacity with respect to mortality, taking as reference the prediction equation developed in the population from which our sample was drawn (SARA). METHODS: We studied 264 patients with chronic obstructive pulmonary disease aged ≥70 years. Agreement was evaluated using the Bland-Altman method, discriminative capacity using incidence rate ratios for mortality calculated across quartiles of each measure. RESULTS: The mean age of the sample was 75.8 years (72.7% men). In women, the mean FEV1ERS/FEV1SARA, FEV1NHANES/ FEV1SARA, and FEV1GLI/FEV1SARA were 0.81, 0.91, and 0.966, respectively. The corresponding values in men were 0.959, 0.963, and 1.02, respectively. The overall discriminative capacity with respect to death was equally poor for all equations. CONCLUSION: The GLI equations for predicting FEV1 provide similar estimates compared to an equation developed in a healthy subset of the population in which they are applied, and higher values compared to the ERS equation, especially in women. However, the use of the GLI equation does not improve the stratification of the risk of mortality in elderly people compared to ERS or NHANES equations.
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Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Volume Expiratório Forçado , Humanos , Itália/epidemiologia , Masculino , Inquéritos Nutricionais , Medição de RiscoRESUMO
We aimed at exploring whether the prevalence of co-morbidities of chronic obstructive pulmonary disease (COPD) increases with COPD severity. Analysis of medical records of outpatients with established diagnosis of COPD was retrospectively performed. The lower limit of normality (LLN) for FEV1/FVC was applied to establish the occurrence of airway obstruction in the elderly population. The prevalence of co-morbidities was calculated, and the proportion of patients with each co-morbidity along with GOLD stages was analysed by chi-square for trend. A total of 326 (M/F: 256/70) consecutive outpatients with COPD (stage GOLD I to IV), aging 71.8 ± 9.2 years, were included in the analysis. The most frequent co-morbidities in the entire sample were systemic hypertension (64.7%), diabetes (28.5%), coronary artery disease (19.9%), arrhythmias (16.6%) and congestive heart failure (13.8%). Underweight patients were 8.0% of the sample while obese patients were 22.4%. None of the analyzed co-morbidities showed a trend towards increasing prevalence with COPD severity, except for nutritional problems. The current findings suggest that the occurrence and prevalence of co-morbidities is independent from the COPD severity, and encourage to assess co-morbidities even in the early stages of the COPD.
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Doença Pulmonar Obstrutiva Crônica/epidemiologia , Índice de Gravidade de Doença , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Estudos RetrospectivosRESUMO
Bronchial asthma is one of the most common chronic diseases worldwide, and by definition not expected to recover with aging. However, the concept that asthma can affect older individuals has been largely denied in the past. In clinical practice, asthma that occurs in the most advanced ages is often diagnosed as COPD, thus leading to undertreatment or improper treatment. The heterogeneity of clinical and functional presentation of geriatric asthma, including the partial loss of reversibility and of the allergic component, contributes to this misconception. A large body of evidence has accumulated demonstrating that the prevalence of asthma in the most advanced ages is similar to that in younger ages. The frequent coexistence of comorbid conditions in older patients compared to younger asthmatics, together with age-associated changes of the human lung, may render the management of asthma a complicated task. The article addresses the main issues related to the diagnosis and treatment of asthma in the geriatric age.
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Asma/diagnóstico , Fatores Etários , Idoso , Antiasmáticos/uso terapêutico , Asma/epidemiologia , Asma/terapia , Comorbidade , Humanos , Adesão à MedicaçãoRESUMO
BACKGROUND AND OBJECTIVE: We aimed to explore to what extent an unselected population of chronic obstructive pulmonary disease (COPD) outpatients would be eligible for inclusion in randomized clinical trials (RCTs). METHODS: Retrospective analysis of the clinical records of outpatient subjects with an ascertained diagnosis of COPD. COPD outpatients were assessed against the following inclusion criteria: 40 < age < 80 years, current or former smokers, forced expiratory volume in the first second (FEV1) <70% predicted, no long-term oxygen therapy, no other concomitant lung diseases and absence of major extrapulmonary comorbidities. The study consisted of 2 phases; in phase 1, the criteria for inclusion in RCTs on COPD were selected, and in phase 2, the above criteria were applied to an unselected outpatient COPD population. RESULTS: A total of 578 subjects (83% of the whole group) failed at least one of the inclusion criteria. Lung diseases other than COPD (occurring in 30% of our population, mostly bronchiectasis), long-term oxygen therapy (31%), FEV1 (19%), age (14%) and extrapulmonary comorbidities such as cognitive impairment (14%), arrhythmias (17%) and congestive heart disease (13%) would have been the most frequent causes for exclusion from RCTs. CONCLUSIONS: In real-life settings, more than 80% of COPD subjects are currently treated by protocols based on results of RCTs for which they would not have been eligible. We encourage a more extensive use of pragmatic trials in COPD to better modulate the application of results of RCTs to patients encountered in daily practice.
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Seleção de Pacientes , Ensaios Clínicos Pragmáticos como Assunto/normas , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bronquiectasia/epidemiologia , Transtornos Cognitivos/epidemiologia , Estudos de Coortes , Comorbidade , Feminino , Volume Expiratório Forçado , Humanos , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Estudos Retrospectivos , Fumar/epidemiologiaRESUMO
BACKGROUND: a multidimensional approach-the BODE index-has been proposed for prognostic purposes in chronic obstructive pulmonary disease (COPD) and theoretically seems to be well suited for elderly people, but there is a lack of data in this population, especially with respect to long-term survival. The objective of this study is to evaluate whether the BODE index can predict both long (5 years) and very-long (10 and 15 years)-term mortality in an unselected population of elderly people with COPD better than a set of variables commonly taken into account in a geriatric multidimensional assessment (MDA). METHODS: : this was a multicentre, prospective, population study. We used data from the SaRA study, which included 563 elderly people with COPD whose vital status was ascertained for up to 15 years after enrolment. The discriminative capacity of the BODE index in predicting mortality was derived from Cox proportional hazard models including the components of the BODE index and compared with that of an alternative model based on MDA variables: age, gender, physical disability, cognitive function and mood status. RESULTS: : at 5 years, the HRs for mortality were 1.04 (95% CI: 0.60-1.79), 1.88 (1.10-3.22) and 3.55 (2.15-5.86) for quartiles 2-4, respectively, compared with quartile 1 of the BODE index. The corresponding figures for 10-year mortality were 1.50 (1.01-2.24), 2.11 (1.39-3.20) and 3.903 (2.62-5.82), and for 15-year mortality were 1.68 (1.19-2.36), 2.08 (1.44-3.01) and 3.78 (2.64-5.41). Similar results were obtained using variables included in the usual MDA. CONCLUSIONS: : Both the 'classic' MDA and the BODE index are comparably associated with mortality, even at very long term, in elderly people with COPD.
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Avaliação Geriátrica/métodos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Itália , Estudos Longitudinais , Masculino , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Testes de Função Respiratória , Taxa de SobrevidaRESUMO
Asthma is a disease of all ages. This assumption has been challenged in the past, because of several cultural and scientific biases. A large body of evidence has accumulated in recent years to confirm that the prevalence of asthma in the most advanced ages is similar to that in younger ages. Asthma in the elderly may show similar functional and clinical characteristics to that occurring in young adults, although the frequent coexistence of comorbid conditions in older patients, together with age-associated changes in the human lung, may lead to more severe forms of the disease. Management of asthma in the elderly follows specific guidelines that apply to all ages, although most behaviors are pure extrapolation of what has been tested in young ages. In fact, age has always represented an exclusion criterion for eligibility to clinical trials. This review focuses specifically on the safety and efficacy of leukotriene modifiers, which represent a valid option in the treatment of allergic asthma, both as an alternative to first-line drugs and as add-on treatment to inhaled corticosteroids. Available studies specifically addressing the role of montelukast in the elderly are scarce; however, leukotriene modifiers have been demonstrated to be safe in this age group, even though cases of acute hepatitis and occurrence of Churg-Strauss syndrome have been described in elderly patients; whether this is associated with age is to be confirmed. Furthermore, leukotriene modifiers provide additional benefit when added to regular maintenance therapy, not differently from young asthmatics. In elderly patients, the simpler route of administration of leukotriene modifiers, compared with the inhaled agents, could represent a more effective strategy in improving the outcomes of asthma therapy, given that unintentional nonadherence with inhalation therapy represents a complex problem that may lead to significant impairment of asthma symptom control.
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Acetatos/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Quinolinas/uso terapêutico , Acetatos/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antiasmáticos/efeitos adversos , Ciclopropanos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quinolinas/efeitos adversos , SulfetosRESUMO
BACKGROUND: Clinical and epidemiologic evidence on asthma in the elderly is scant. There is evidence that forced expiratory volume in the first second (FEV1), a commonly used indicator of overall pulmonary function, might not be an independent predictor of 5-year mortality in elderly patients with asthma. OBJECTIVE: To investigate the association between FEV1 expressed using 3 alternative methods and 5-, 10-, and 15-year mortality in a population of elderly patients with asthma. METHODS: Participants in the Salute Respiratoria nell' Anziano study were included. Asthma was diagnosed at baseline according to spirometric and clinical data. Vital status at 15 years was assessed using death registries. FEV1 was expressed as percentage of predicted, divided by height cubed, and as a multiple of the sex-specific first percentile. The association between FEV1 and mortality was evaluated using Cox proportional hazard models. RESULTS: Two hundred patients were studied (52% women, mean age 73.1 years, standard deviation 6.2 years). All FEV1 measurements were associated with mortality at unadjusted analysis. After correction for potential confounders, no association was found between FEV1 and 5-year mortality. Only FEV1 as a multiple of the sex-specific first percentile was independently associated with 10-year (hazard ratio 0.35, 95% confidence interval 0.14-0.87) and 15-year (hazard ratio 0.38, 95% confidence interval 0.19-0.79) mortality. CONCLUSION: Although extensively used, FEV1 expressed as percentage of predicted does not seem to be the best predictor of mortality in elderly patients with asthma. Although no spirometric index can predict 5-year mortality in this population, FEV1 as a multiple of the sex-specific first percentile should be considered when longer-term prognostic stratification is needed.
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Asma/mortalidade , Asma/fisiopatologia , Volume Expiratório Forçado , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Prognóstico , Testes de Função Respiratória , EspirometriaRESUMO
BACKGROUND: The levels of serum low-density lipoproteins (LDL) have been implicated in the inflammatory cascade in a murine model of asthma. Recent findings suggest that LDL may modulate the inflammatory state of the asthmatic airways in humans. OBJECTIVE: We explored whether LDL subclasses are associated with the occurrence and severity of asthma. METHODS: 24 asthmatics (M/F: 11/13) and 24 healthy individuals, with normal BMI and absence of metabolic syndrome, matched for age and gender. Serum concentrations of LDL subclasses were distributed as seven bands (LDL-1 and -2 defined as large, least pro-inflammatory LDL, and LDL-3 to -7 defined as small, most pro-inflammatory LDL), using the LipoPrint(©) System (Quantimetrix Corporation, Redondo Beach, CA, USA). RESULTS: LDL-1 was similar in the two groups (56 ± 16% vs. 53 ± 11, p = NS), while LDL-2 was significantly lower in asthmatics as compared to controls (35 ± 8% vs. 43 ± 10%, p = 0.0074). LDL-3 levels were two-fold higher in the asthmatics, but the difference did not reach the statistical significance (8 ± 7.3% vs. 4 ± 3%, p = NS). Smaller subclasses LDL-4 to LDL-7 were undetectable in controls. In asthmatics, LDL-1 was positively associated with VC% predicted (r = +0.572, p = 0.0035) and FEV1% predicted (r = +0.492, p = 0.0146). LDL-3 was inversely correlated with both VC% predicted (r = -0.535, p = 0.0071) and FEV1% predicted (r = -0.465, p = 0.0222). CONCLUSIONS: The findings of this pilot study suggest a role of LDL in asthma, and advocate for larger studies to confirm the association between asthma and dyslipidemia.
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Asma/etiologia , Hipolipoproteinemias/complicações , Lipoproteínas LDL/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/sangue , Asma/classificação , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Hipolipoproteinemias/sangue , Lipoproteínas LDL/classificação , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Capacidade Vital/fisiologiaRESUMO
BACKGROUND: Allergic diseases impair health-related quality of life (HR-QoL). However, the relationship between airway inflammation and HR-QoL in patients with asthma and rhinitis has not been fully investigated. We explored whether the inflammation of upper and lower airways is associated with HR-QoL. METHODS: Twenty-two mild allergic asthmatics with concomitant rhinitis (10 males, 38 ± 17 years) were recruited. The Rhinasthma was used to identify HR-QoL, and the Asthma Control Test (ACT) was used to assess asthma control. Subjects underwent lung function and exhaled nitric oxide (eNO) test, collection of exhaled breath condensate (EBC), and nasal wash. RESULTS: The Rhinasthma Global Summary score (GS) was 25 ± 11. No relationships were found between GS and markers of nasal allergic inflammation (% eosinophils: r = 0.34, P = 0.24; ECP: r = 0.06, P = 0.87) or bronchial inflammation (pH of the EBC: r = 0.12, P = 0.44; bronchial NO: r = 0.27, P = 0.22; alveolar NO: r = 0.38, P = 0.10). The mean ACT score was 18. When subjects were divided into controlled (ACT ≥ 20) and uncontrolled (ACT < 20), the alveolar NO significantly correlated with GS in uncontrolled asthmatics (r = 0.60, P = 0.04). CONCLUSIONS: Upper and lower airways inflammation appears unrelated to HR-QoL associated with respiratory symptoms. These preliminary findings suggest that, in uncontrolled asthma, peripheral airway inflammation could be responsible for impaired HR-QoL.
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Asma/complicações , Asma/patologia , Saúde , Inflamação/complicações , Inflamação/patologia , Pulmão/patologia , Qualidade de Vida , Adulto , Asma/fisiopatologia , Biomarcadores/metabolismo , Feminino , Humanos , Inflamação/fisiopatologia , Pulmão/fisiopatologia , Masculino , Óxido Nítrico/metabolismo , Alvéolos Pulmonares/metabolismo , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/fisiopatologia , Testes de Função Respiratória , Inquéritos e QuestionáriosAssuntos
Asma/metabolismo , Asma/prevenção & controle , Expiração , Óxido Nítrico , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: We hypothesized that changes in the levels of sexual hormones during the menstrual cycle influence the concentration of nitric oxide in the exhaled air (FeNO) and alveolar exhaled nitric oxide (CANO). METHODS: Twelve healthy, non allergic women in their reproductive age (age range 25-37 years) were recruited. Subjects were studied, on alternate days, over the course of their menstrual cycle. At each visit, measurements of FeNO and CANO were performed. Progesterone and 17-ß-estradiol concentrations were measured in salivary samples. RESULTS: Eight subjects completed the study. The levels of FeNO and CANO were 13 ± 4.7 pbb and 3.5 ± 1.9 pbb, respectively (mean ± SD). The mean salivary concentration of progesterone was 65.1 ± 16.2 pg/ml (mean ± SD), with a range of 32.4-107.7 pg/ml, and the concentration of 17 ß-estradiol was 6.0 ± 1.6 pg/ml, with a range of 3.1-12.9 pg/ml. The Generalized Estimating Equations procedure demonstrated that levels of progesterone influenced both FeNO and CANO (Wald χ2 = 11.60, p = 0.001; and Wald χ2 = 87.55, p = 0.001, respectively). On the contrary, the salivary levels of 17 ß-estradiol were not significantly associated with FeNO (Wald χ2 = 0.087, p = 0.768) or CANO (Wald χ2 = 0.58, p = 0.448). CONCLUSION: In healthy women, the menstrual cycle-associated hormonal fluctuations selectively influence the levels of bronchial and alveolar NO. The current findings may have important clinical implications for the interpretation of eNO levels, by identifying a patient-related factor that influences the eNO measurements.
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Estradiol/análise , Ciclo Menstrual/fisiologia , Óxido Nítrico/análise , Progesterona/análise , Adulto , Testes Respiratórios , Brônquios/metabolismo , Estradiol/metabolismo , Feminino , Humanos , Óxido Nítrico/metabolismo , Progesterona/metabolismo , Alvéolos Pulmonares/metabolismo , Saliva/fisiologiaRESUMO
BACKGROUND: The role of the peripheral airways in asthma is increasingly being recognized as a potential target for the achievement of optimal control of the disease. We postulated that the inflammatory changes of the small airways are implicated in the lack of asthma control in mild asthma. OBJECTIVE: To test this hypothesis, we measured the alveolar fraction of exhaled NO (CalvNO) in patients with mild asthma with different levels of control of symptoms. METHODS: Seventy-eight patients with asthma (35 men, age, 37 ± 15 years; FEV1 percentage of predicted, 100% ± 9%) were studied. Asthma control was assessed by using the Asthma Control Test (ACT). Measurements of exhaled NO at multiple constant flows were performed. RESULTS: Bronchial NO concentrations were 27.1 ± 20 nL/min, [corrected] and CalvNO levels were 5.7 ± 3.4 ppb. The ACT score was 20 ± 4.2. The level of asthma control was not associated with bronchial NO concentrations (rs = 0.16, P = .15). However, a significant correlation was found between the ACT score and CalvNO (rs = 0.25, P = .03). Moreover, CalvNO was significantly higher in patients with uncontrolled asthma than in patients with controlled/partially controlled asthma (6.7 ± 2.6 ppb vs 4.9 ± 2.6 nL/min, [corrected] respectively, P = .02). In the subgroup of patients with asthma who underwent extrafine inhaled corticosteroid treatment, the magnitude of the inhaled corticosteroid-induced improvement in asthma control positively correlated with baseline CalvNO at 1 month (rs = 0.39, P = .003) and at 3 months (rs = 0.49, P < .0001). CONCLUSIONS: The alveolar component of exhaled NO is associated with the lack of asthma control in patients with mild, untreated asthma. This observation supports the notion that abnormalities of the peripheral airways are implicated in the mildest forms of asthma.
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Asma/metabolismo , Asma/prevenção & controle , Expiração , Óxido Nítrico , Adulto , Asma/fisiopatologia , Feminino , Humanos , Masculino , Testes de Função Respiratória , Adulto JovemRESUMO
INTRODUCTION: Decreased airway distensibility (AD) in response to deep inspirations, as assessed by HRCT, has been associated with the severity of asthma and COPD. AIMS: The current study was designed to compare the magnitude of AD by HRCT in individuals with asthma and COPD with comparable degrees of bronchial obstruction, and to explore factors that may influence it. RESULTS: We enrolled a total of 12 asthmatics (M/F:7/5) and 8 COPD (7/1) with comparable degree of bronchial obstruction (FEV1% predicted mean ± SEM: 69.1 ± 5.2% and 61.2 ± 5.0%, respectively; p = 0.31). Each subject underwent chest HRCT at FRC and at TLC. A total of 701 airways (range 20 to 38 airway per subject; 2.0 to 23.1 mm in diameter) were analyzed. AD did not differ between asthmatics and COPD (mean ± SEM: 14 ± 3.5% and 17 ± 4.3%, respectively; p = 0.58). In asthmatics, AD was significantly associated with FEV1% predicted (r(2) = 0.45, p = 0.018). We found a significant correlation between the change in lung volume and the change in AD by HRCT (r(2) = 0.64, p = 0.002). In COPD, we found significant correlations between AD and the RV% predicted (r(2) = 0.51, p = 0.046) and the RV/TLC (r(2) = 0.68, p = 0.01). CONCLUSIONS: AD was primarily affected by the dynamic ability to change lung volumes in asthmatics, and by static lung volumes in COPD.
Assuntos
Asma/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Adulto , Idoso , Feminino , Volume Expiratório Forçado , Humanos , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Espirometria , Capacidade VitalRESUMO
OBJECTIVE: The ultra-short course preseasonal allergy vaccine, containing the adjuvant monophosphoryl lipid A (MPL), is effective in treating allergic symptoms; however, the efficacy in controlling asthmatics symptoms has not been fully demonstrated. We aimed at evaluating whether the ultra-short preseasonal course of immunotherapy contributes to asthma control. METHODS: Four subcutaneous injections of the active product (Pollinex Quattro) were administered, before the pollen season, to 20 Parietaria-sensitive mild, untreated asthmatics (M/F: 12/8; age: 38 ± 14 years). After the screening visit (visit 1), asthma control was assessed by the Asthma Control Test (ACT) immediately before the first (visit 2) and immediately after the last (visit 5) injections, as well as during the pollen season (visit 6). Bronchial and alveolar exhaled nitric oxide (NO) concentrations were also measured. Nine Parietaria-sensitive mild asthmatics (M/F: 3/6; age: 40 ± 12 years) served as untreated controls. RESULTS: The ACT remained constant during allergen exposure in specific immunotherapy (SIT)-treated asthmatics (visit 2: 22 ± 3.2; visit 5: 23 ± 2.8; visit 6: 22 ± 3.6; analysis of variance [ANOVA], p = 0.47), whereas it dropped during pollen exposure in controls (visit 2: 20 ± 2.5; visit 5: 21 ± 2.8; visit 6: 16 ± 5.7; ANOVA, p = 0.01). The forced expiratory NO (FENO) values significantly increased during pollen exposure in both groups; however, the alveolar NO concentrations remained stable in SIT-treated asthmatics (p = 0.11), whereas they doubled in controls (p = 0.01). CONCLUSIONS: The current findings show that the preseasonal vaccine adjuvated with MPL contributes to the maintenance of control of asthma during the pollen season.
Assuntos
Asma/terapia , Inflamação/terapia , Parietaria/imunologia , Vacinas/imunologia , Adulto , Asma/fisiopatologia , Testes Respiratórios , Dessensibilização Imunológica , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/análiseRESUMO
The mainstay of management in asthma is inhalation therapy at the target site, with direct delivery of the aerosolized drug into the airways to treat inflammation and relieve obstruction. Abundant evidence is available to support the concept that inflammatory and functional changes at the level of the most peripheral airways strongly contribute to the complexity and heterogeneous manifestations of asthma. It is now largely accepted that there is a wide range of clinical phenotypes of the disease, characterized primarily by small airways involvement. Thus, an appropriate diagnostic algorithm cannot exclude biological and functional assessment of the peripheral airways. Similarly, achievement of optimal control of the disease and appropriate management of specific phenotypes of asthma should be based on drugs (and delivery options) able to distribute uniformly along the bronchial tree and to reach the most peripheral airways. Products developed with the Modulite(®) technology platform have been demonstrated to meet these aims. Recent real-life studies have shown clearly that extra-fine fixed-combination inhaled therapy provides better asthma control than non-extra-fine formulations, thus translating the activity of the drugs into greater effectiveness in clinical practice. We suggest that in patients with incomplete asthma control despite good lung function, involvement of the peripheral airways should always be suspected. When this is the case, treatments targeting both the large and small airways should be used to improve asthma control. Above all, it is emphasized that patient adherence with prescribed medications can contribute to clinical success, and clinicians should always be aware of the role played by patients themselves in determining the success or failure of treatment.
RESUMO
Expressing forced expiratory volume in 1 s (FEV1) as % predicted relies on the assumption of proportional variability and generalisability of prediction equations that may be unrealistic, especially for elderly people. We evaluated the prognostic implications of alternative ways of expressing FEV1. We enrolled 318 patients with chronic obstructive pulmonary disease (COPD) and 475 controls in the Salute Respiratoria nell'Anziano (SARA) study. The risk for 5-, 10- and 15-year mortality associated with FEV1 was studied by expressing FEV1 % pred, standardised by height cubed (FEV1 · Ht(-3)) and as a multiple of the sex-specific first percentile (FEV1 quotient (FEV1Q)). In the group with COPD, the incidence rate ratio for the worst versus the best quintile of FEV1Q was 4.65 (95% CI 2.33-10.37), compared to 2.98 (1.53-6.27) for FEV1 % pred and 3.95 (2.01-8.45) for FEV1 · Ht(-3). The corresponding incidence rate ratios at 15 years were 4.52 (2.84-7.43), 3.16 (2.02-5.07) and 3.52 (2.25-5.63), respectively. In the control group, even moderate reduction of FEV1Q was associated with long-term mortality, while FEV1 % pred was not associated with the outcome. FEV1Q may be more informative about prognosis in an elderly population compared to FEV1 % pred.
Assuntos
Volume Expiratório Forçado , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/mortalidade , Testes de Função Respiratória/métodos , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Espirometria/métodos , Resultado do TratamentoRESUMO
BACKGROUND: The choice between lower limit of normal or fixed value of forced expiratory volume in one second/forced vital capacity ratio (FEV(1)/FVC) < 0.70 as the criterion for confirming airway obstruction is an open issue. In this study, we compared the criteria of lower limit of normal and fixed FEV(1)/FVC for diagnosis of airway obstruction, with a focus on healthy elderly people. METHODS: We selected 367 healthy nonsmoking subjects aged 65-93 years from 1971 participants in the population-based SARA (Salute Respiratoria nell'Anziano, Italian for "Respiratory Health in the Elderly") study, analyzed their spirometric data, and tested the relationship between spirometric indices and anthropometric variables. The lower limit of normal for FEV(1)/FVC was calculated as the fifth percentile of the normal distribution for selected subjects. RESULTS: While FEV(1) and FVC decreased significantly with aging, the relationship between FEV(1)/FVC and age was not statistically significant in men or women. The lower limit of normal for FEV(1)/FVC was 0.65 in men and 0.67 in women. Fifty-five participants (15%) had FEV(1)/FVC < 0.70 and would have been inappropriately classified as obstructed according to the Global Initiative for Obstructive Lung Disease, American Thoracic Society/European Respiratory Society, and Canadian guidelines on chronic obstructive pulmonary disease. By applying different FEV(1)/FVC thresholds for the different age groups, as previously proposed in the literature, (0.70 for <70 years, 0.65 for 70-80 years, and 0.60 for >80 years) the percentage of patients classified as obstructed decreased to 6%. No subjects older than 80 years had an FEV(1)/FVC < 0.60. CONCLUSION: The present results confirm the inadequacy of FEV(1)/FVC < 0.70 as a diagnostic criterion for airway obstruction after the age of 65 years. FEV(1)/FVC < 0.65 and <0.67 (for men and women, respectively) could identify subjects with airway obstruction in such a population. Further reduction of the threshold after 80 years is not justified.