Progressive fibrotic interstitial lung disease.

Many interstitial lung diseases (ILDs) share mechanisms that result in a progressive fibrosing phenotype. In Brazil, the most common progressive fibrosing interstitial lung diseases (PF-ILDs) are chronic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, unclassified ILD, and connective tissue diseases. PF-ILD is seen in approximately 30% of patients with ILD. Because PF-ILD is characterized by disease progression after initiation of appropriate treatment, a diagnosis of the disease resulting in fibrosis is critical. Different criteria have been proposed to define progressive disease, including worsening respiratory symptoms, lung function decline, and radiological evidence of disease progression. Although the time elapsed between diagnosis and progression varies, progression can occur at any time after diagnosis. Several factors indicate an increased risk of progression and death. In the last few years, antifibrotic drugs used in patients with idiopathic pulmonary fibrosis have been tested in patients with PF-ILD. The effects of nintedanib and placebo have been compared in patients with PF-ILD, a mean difference of 107.0 mL/year being observed, favoring nintedanib. The U.S. Food and Drug Administration and the Brazilian Health Regulatory Agency have approved the use of nintedanib in such patients on the basis of this finding. Pirfenidone has been evaluated in patients with unclassified ILD and in patients with other ILDs, the results being similar to those for nintedanib. More studies are needed in order to identify markers of increased risk of progression in patients with ILD and determine the likelihood of response to treatment with standard or new drugs.

Progressive fibrotic interstitial lung disease / Doença pulmonar intersticial fibrosante progressiva

ABSTRACT Many interstitial lung diseases (ILDs) share mechanisms that result in a progressive fibrosing phenotype. In Brazil, the most common progressive fibrosing interstitial lung diseases (PF-ILDs) are chronic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, unclassified ILD, and connective tissue diseases. PF-ILD is seen in approximately 30% of patients with ILD. Because PF-ILD is characterized by disease progression after initiation of appropriate treatment, a diagnosis of the disease resulting in fibrosis is critical. Different criteria have been proposed to define progressive disease, including worsening respiratory symptoms, lung function decline, and radiological evidence of disease progression. Although the time elapsed between diagnosis and progression varies, progression can occur at any time after diagnosis. Several factors indicate an increased risk of progression and death. In the last few years, antifibrotic drugs used in patients with idiopathic pulmonary fibrosis have been tested in patients with PF-ILD. The effects of nintedanib and placebo have been compared in patients with PF-ILD, a mean difference of 107.0 mL/year being observed, favoring nintedanib. The U.S. Food and Drug Administration and the Brazilian Health Regulatory Agency have approved the use of nintedanib in such patients on the basis of this finding. Pirfenidone has been evaluated in patients with unclassified ILD and in patients with other ILDs, the results being similar to those for nintedanib. More studies are needed in order to identify markers of increased risk of progression in patients with ILD and determine the likelihood of response to treatment with standard or new drugs.

RESUMO Muitas doenças pulmonares intersticiais (DPI) compartilham mecanismos que resultam em um fenótipo fibrosante progressivo. No Brasil, as doenças pulmonares intersticiais fibrosantes progressivas (DPI-FP) mais comuns são a pneumonite de hipersensibilidade crônica, a fibrose pulmonar idiopática, a DPI não classificada e as doenças do tecido conjuntivo. A DPI-FP é observada em aproximadamente 30% dos pacientes com DPI. Como a DPI-FP é caracterizada pela progressão da doença após o início do tratamento adequado, é fundamental diagnosticar a doença que resulta em fibrose. Diferentes critérios foram propostos para definir doença progressiva, incluindo piora dos sintomas respiratórios, declínio da função pulmonar e evidências radiológicas de progressão da doença. Embora o tempo decorrido entre o diagnóstico e a progressão varie, a progressão pode ocorrer a qualquer momento após o diagnóstico. Vários fatores indicam risco aumentado de progressão e morte. Nos últimos anos, antifibróticos usados em pacientes com fibrose pulmonar idiopática foram testados em pacientes com DPI-FP. Os efeitos do nintedanibe e placebo foram comparados em pacientes com DPI-FP, com diferença média de 107,0 mL/ano a favor do nintedanibe. A Food and Drug Administration (EUA) e a Agência Nacional de Vigilância Sanitária aprovaram o uso do nintedanibe em tais pacientes com base nesse achado. A pirfenidona foi avaliada em pacientes com DPI não classificada e em pacientes com outras DPI, e os resultados foram semelhantes aos do nintedanibe. Mais estudos são necessários para identificar marcadores de risco aumentado de progressão em pacientes com DPI e determinar a probabilidade de resposta ao tratamento com medicamentos-padrão ou novos.

Executive Summary: Diagnosis and Evaluation of Hypersensitivity Pneumonitis: CHEST Guideline and Expert Panel Report.

BACKGROUND: The purpose of this summary is to provide a synopsis of evidence-based and consensus-derived guidance for clinicians to improve individual diagnostic decision-making for hypersensitivity pneumonitis (HP) and decrease diagnostic practice variability. STUDY DESIGN AND METHODS: Approved panelists developed key questions regarding the diagnosis of HP using the PICO (Population, Intervention, Comparator, and Outcome) format. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion and vetted evaluation tools were used to assess the quality of included studies, to extract data, and to grade the level of evidence supporting each recommendation or statement. The quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted and voted on using a modified Delphi technique to achieve consensus. RESULTS: The systematic review of the literature based on 14 PICO questions resulted in 14 key action statements: 12 evidence-based, graded recommendations, and 2 ungraded consensus-based statements. All evidence was of very low quality. INTERPRETATION: Diagnosis of HP should employ a patient-centered approach and include a multidisciplinary assessment that incorporates the environmental and occupational exposure history and CT pattern to establish diagnostic confidence prior to considering BAL and/or lung biopsy. Additional research is needed on the performance characteristics and generalizability of exposure assessment tools and traditional and new diagnostic tests in modifying clinical decision-making for HP, particularly among those with a provisional diagnosis.

Diagnosis and Evaluation of Hypersensitivity Pneumonitis: CHEST Guideline and Expert Panel Report.

BACKGROUND: The purpose of this analysis is to provide evidence-based and consensus-derived guidance for clinicians to improve individual diagnostic decision-making for hypersensitivity pneumonitis (HP) and decrease diagnostic practice variability. STUDY DESIGN AND METHODS: Approved panelists developed key questions regarding the diagnosis of HP using the PICO (Population, Intervention, Comparator, Outcome) format. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion, and vetted evaluation tools were used to assess the quality of included studies, to extract data, and to grade the level of evidence supporting each recommendation or statement. The quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted and voted on using a modified Delphi technique to achieve consensus. A diagnostic algorithm is provided, using supporting data from the recommendations where possible, along with expert consensus to help physicians gauge the probability of HP. RESULTS: The systematic review of the literature based on 14 PICO questions resulted in 14 key action statements: 12 evidence-based, graded recommendations and 2 ungraded consensus-based statements. All evidence was of very low quality. INTERPRETATION: Diagnosis of HP should employ a patient-centered approach and include a multidisciplinary assessment that incorporates the environmental and occupational exposure history and CT pattern to establish diagnostic confidence prior to considering BAL and/or lung biopsy. Criteria are presented to facilitate diagnosis of HP. Additional research is needed on the performance characteristics and generalizability of exposure assessment tools and traditional and new diagnostic tests in modifying clinical decision-making for HP, particularly among those with a provisional diagnosis.

Uncovering the mechanisms of exertional dyspnoea in combined pulmonary fibrosis and emphysema.

The prevailing view is that exertional dyspnoea in patients with combined idiopathic pulmonary fibrosis (IPF) and emphysema (CPFE) can be largely explained by severe hypoxaemia. However, there is little evidence to support these assumptions.We prospectively contrasted the sensory and physiological responses to exercise in 42 CPFE and 16 IPF patients matched by the severity of exertional hypoxaemia. Emphysema and pulmonary fibrosis were quantified using computed tomography. Inspiratory constraints were assessed in a constant work rate test: capillary blood gases were obtained in a subset of patients.CPFE patients had lower exercise capacity despite less extensive fibrosis compared to IPF (p=0.004 and 0.02, respectively). Exertional dyspnoea was the key limiting symptom in 24 CPFE patients who showed significantly lower transfer factor, arterial carbon dioxide tension and ventilatory efficiency (higher minute ventilation (V'E)/carbon dioxide output (V'CO2 ) ratio) compared to those with less dyspnoea. However, there were no between-group differences in the likelihood of pulmonary hypertension by echocardiography (p=0.44). High dead space/tidal volume ratio, low capillary carbon dioxide tension emphysema severity (including admixed emphysema) and traction bronchiectasis were related to a high V'E/V'CO2 ratio in the more dyspnoeic group. V'E/V'CO2 nadir >50 (OR 9.43, 95% CI 5.28-13.6; p=0.0001) and total emphysema extent >15% (2.25, 1.28-3.54; p=0.01) predicted a high dyspnoea burden associated with severely reduced exercise capacity in CPFEContrary to current understanding, hypoxaemia per se is not the main determinant of exertional dyspnoea in CPFE. Poor ventilatory efficiency due to increased "wasted" ventilation in emphysematous areas and hyperventilation holds a key mechanistic role that deserves therapeutic attention.

Squawks in interstitial lung disease prevalence and causes in a cohort of one thousand patients.

Squawks are lung adventitious sounds with a mix of both musical and nonmusical components heard during the inspiratory phase. Small series have described squawks in interstitial lung diseases. Hypersensitivity pneumonitis and other diseases involving small airways can result in squawks, but new interstitial lung diseases (ILDs) involving peripheral airways are being described. A retrospective analysis was performed on 1000 consecutive patients from a database of ILD of a tertiary referral center. Squawks were recorded in 49 cases (4.9%), hypersensitivity pneumonitis (23 cases), connective tissue disease (7), microaspiration (4), pleuroparenchymal fibroelastosis (4), fibrosing cryptogenic organizing pneumonia (, 3), familial ILD (2), sarcoidosis (2), idiopathic pulmonary fibrosis (IPF; 1), bronchiolitis (2), and nonspecific interstitial pneumonia (1). One patient had a final diagnosis of IPF. There was a significant association between mosaic pattern and squawks: 20 cases with squawks (40.8%) had mosaic pattern compared with 140 (14.7%) cases without squawks (x = 23.6, P < .001).Findings indicative of fibrosis were described on high-resolution chest tomography (HRCT) in 715 cases (71.5%). Squawks were more common in patients with findings indicative of fibrosis on HRCT: 45 of 715 (6.3%) compared with 4 of 285 (1.4%) of those without findings indicative of fibrosis (x = 10.46, P = .001).In conclusion, squawks are an uncommon finding on physical examination in patients with ILD, but when present suggest fibrosing ILD associated with bronchiolar involvement. However, squawks are rare in IPF.

Change in FVC and survival in chronic fibrotic hypersensitivity pneumonitis.

The predictive value of the decline in FVC by ≥10% on survival in patients with fibrotic hypersensitivity pneumonitis is unknown. Of 112 patients included, 66 (59%) had surgical lung biopsies. Patients with ≥10% decline in predicted FVC after 6-12 months had a significantly increased risk of all-cause mortality (median survival 53 months, 95% CI 37 to 69 vs 139 months, 95% CI 66 to 212 months, p=0.007). On multivariate analysis remained associated with increasing mortality: decline in FVC by ≥10% (HR 4.13, 95% CI 1.96 to 8.70, p=0.005), lower FVC% (HR 1.03, 95% CI 1.01 to 1.05, p=0.003) and with decreasing mortality improvement with antigen avoidance (HR 0.18, 95% CI 0.04 to 0.77, p=0.021).

Diagnostic Approach to Advanced Fibrotic Interstitial Lung Disease: Bringing Together Clinical, Radiologic, and Histologic Clues.

CONTEXT: - Idiopathic pulmonary fibrosis (IPF) is a distinctive clinicopathologic entity and the most common form of progressive diffuse lung scarring in older adults. Idiopathic pulmonary fibrosis manifests histopathologically as the usual interstitial pneumonia pattern. The usual interstitial pneumonia pattern is distinguished by geographically and temporally heterogeneous fibrosis that is peripherally accentuated, often with honeycombing and traction bronchiectasis. Idiopathic pulmonary fibrosis is not the only disease that leads to end-stage lung fibrosis, however, and several other entities may also cause advanced fibrosis. Surgical lung biopsies often present a diagnostic dilemma when they show clear evidence of advanced fibrosis, but the clinical, imaging, and/or histopathologic subcharacteristics suggest something other than IPF. OBJECTIVE: - To address this dilemma, we review several other fibrotic lung diseases, including connective tissue disease-associated interstitial lung disease, chronic hypersensitivity pneumonitis, advanced pulmonary Langerhans cell histiocytosis, end-stage pulmonary sarcoidosis, Erdheim-Chester disease, Hermansky-Pudlak syndrome, and others, detailing their clinical, radiologic, and histopathologic attributes and emphasizing similarities to and differences from IPF. DATA SOURCES: - Data sources comprised published peer-reviewed literature and personal experience of the authors. CONCLUSIONS: - Often, clues in the lung biopsy may offer the first suggestion of a fibrotic lung disease other than IPF, and accurate classification is important for prognosis, treatment, and the development of future therapies.

Clinical phenotypes in sarcoidosis.

PURPOSE OF REVIEW: To describe the methods for derivation of clinical phenotypes in general and how they should be applied in sarcoidosis, taking into account the dimensions of the disease. The results from the small number of studies in this area are summarized. RECENT FINDINGS: Clinical phenotypes are determined by diverse ways. In sarcoidosis, some studies defined clinical phenotypes based on severity of disease and outcome after treatment of variable duration. A second approach to characterize clinical phenotypes is by using analytic or multivariate techniques. This approach considers several domains of disease and does not make assumptions a priori, with the hypothesis being developed after the results. A small study used factorial analysis for this purpose. Some well defined clinical phenotypes are described and future directions for research are given. SUMMARY: Clinical phenotypes, by examining relationships between several domains in sarcoidosis, are likely to better delineate the underlying processes and pathways. Larger studies with appropriate methods should be performed to better delineate clinical phenotypes in sarcoidosis.

A haemodynamic study of pulmonary hypertension in chronic hypersensitivity pneumonitis.

Chronic hypersensitivity pneumonitis is a common fibrotic interstitial lung disease. The prevalence of pulmonary hypertension diagnosed by right heart catheterisation and its cardiopulmonary function findings in patients with chronic hypersensitivity pneumonitis are unknown. Consecutive symptomatic patients with chronic hypersensitivity pneumonitis were prospectively evaluated. All patients were submitted to right heart catheterisation, pulmonary function testing, a 6-min walk test, echocardiography, blood gas determination and N-terminal pro-brain natriuretic peptide analyses. Nonhypoxaemic patients also underwent incremental cardiopulmonary exercise testing. 50 patients underwent right heart catheterisation; 25 (50%) of these had pulmonary hypertension and 22 (44%) had a pre-capillary haemodynamic pattern. The patients with pre-capillary pulmonary hypertension had lower forced vital capacity (mean ± sd 50 ± 17% versus 69 ± 22% predicted, p<0.01), carbon monoxide diffusing capacity (37 ± 12% versus 47 ± 14% predicted, p<0.01), arterial oxygen tension (median (interquartile range) 59.0 (47.8-69.3) versus 73.0 (62.2-78.5) mmHg, p<0.01) and saturation after the 6-min walk test (78 ± 8% versus 86 ± 7%, p<0.01). In pre-capillary pulmonary hypertension, oxygen uptake was also lower at the anaerobic threshold (41 ± 11% versus 50 ± 8% predicted, p=0.04) and at peak exercise (12.8 ± 1.6 versus 15.0 ± 2.5 mL · kg(-1) · min(-1), p=0.02). Pre-capillary pulmonary hypertension is common in symptomatic chronic hypersensitivity pneumonitis and is related to interstitial lung disease severity. Additionally, pulmonary hypertension is more prevalent in hypoxaemic patients with impaired lung function and exercise capacity.

Valores de referência para espirometria em crianças pré-escolares / Reference values for spirometry in preschool children

OBJETIVOS: Valores de referência para testes de função pulmonar diferem em amostras de diferentes países, incluindo valores para pré-escolares. O objetivo principal do presente estudo foi derivar valores de referência em nossa população. MÉTODOS: Foi realizado estudo prospectivo, com aplicação de questionário a 425 crianças pré-escolares com idade variando entre três e seis anos, provenientes de escolas e creches públicas e privadas de uma cidade metropolitana do Brasil. As crianças foram selecionadas por amostragem aleatória simples dos referidos educandários. Foram avaliados: PFE, CVF, VEF1 VEF0,50, FEF25-75 e as relações: VEF1/CVF, VEF0,5/CVF e FEF25-75/CVF. RESULTADOS: Das 425 crianças recrutadas, 321 (75,6%) realizaram os testes. Destas, 135 (42,0%) apresentaram manobras aceitáveis, com curvas expiratórias completas e fizeram parte da análise de regressão para definir os valores de referência. Por análise de regressão linear e logarítmica, a estatura e o sexo influenciaram significativamente nas medidas de CVF. No sexo masculino, o r² se elevou com o modelo logarítmico, para a CVF e VEF1, porém o modelo linear foi mantido, por sua simplicidade. Os limites inferiores foram calculados através das medidas do 5º percentil dos resíduos. CONCLUSÃO: Curvas expiratórias completas são de mais difícil obtenção em pré-escolares. Além da estatura, o sexo também influencia nas medidas de CVF e VEF1. Foram definidos valores de referência para espirometria em crianças pré-escolares, nessa população, aplicáveis a populações semelhantes.

OBJECTIVES: Reference values for lung function tests differ in samples from different countries, including values for preschoolers. The main objective of this study was to derive reference values in this population. METHODS: A prospective study was conducted through a questionnaire applied to 425 preschool children aged 3 to 6 years, from schools and day-care centers in a metropolitan city in Brazil. Children were selected by simple random sampling from the aforementioned schools. Peak expiratory flow (PEF), forced vital capacity (FVC), forced expiratory volumes (FEV1, FEV0.50), forced expiratory flow (FEF25-75) and FEV1/FVC, FEV0.5/FVC and FEF25-75/FVC ratios were evaluated. RESULTS: Of the 425 children enrolled, 321 (75.6%) underwent the tests. Of these, 135 (42.0%) showed acceptable results with full expiratory curves and thus were included in the regression analysis to define the reference values. Height and gender significantly influenced FVC values through linear and logarithmic regression analysis. In males, R2 increased with the logarithmic model for FVC and FEV1, but the linear model was retained for its simplicity. The lower limits were calculated by measuring the fifth percentile residues. CONCLUSION: Full expiratory curves are more difficult to obtain in preschoolers. In addition to height, gender also influences the measures of FVC and FEV1. Reference values were defined for spirometry in preschool children in this population, which are applicable to similar populations.

Reference values for spirometry in preschool children.

OBJECTIVES: Reference values for lung function tests differ in samples from different countries, including values for preschoolers. The main objective of this study was to derive reference values in this population. METHODS: A prospective study was conducted through a questionnaire applied to 425 preschool children aged 3 to 6 years, from schools and day-care centers in a metropolitan city in Brazil. Children were selected by simple random sampling from the aforementioned schools. Peak expiratory flow (PEF), forced vital capacity (FVC), forced expiratory volumes (FEV1, FEV0.50), forced expiratory flow (FEF25-75) and FEV1/FVC, FEV0.5/FVC and FEF25-75/FVC ratios were evaluated. RESULTS: Of the 425 children enrolled, 321 (75.6%) underwent the tests. Of these, 135 (42.0%) showed acceptable results with full expiratory curves and thus were included in the regression analysis to define the reference values. Height and gender significantly influenced FVC values through linear and logarithmic regression analysis. In males, R(2) increased with the logarithmic model for FVC and FEV1, but the linear model was retained for its simplicity. The lower limits were calculated by measuring the fifth percentile residues. CONCLUSION: Full expiratory curves are more difficult to obtain in preschoolers. In addition to height, gender also influences the measures of FVC and FEV1. Reference values were defined for spirometry in preschool children in this population, which are applicable to similar populations.

Sarcoidosis Masquerading as Atrial Fibrillation: Interesting Case Discussion as Well as Recent Advances in Diagnosis and Management of Cardiac Sarcoidosis.

This report presents a case of cardiac sarcoidosis initially manifested with atrial fibrillation. This behavior is very uncommon in spite of the fact that the disease is multisystemic, affecting predominantly the lungs. It is emphasized that the diagnosis of the cardiac involvement is difficult, and when this occurs, can lead to conducting system disturbances, heart failure or sudden death (SD). The diagnosis can be made by evaluating the clinical manifestations, the noninvasive tests like ECG, Holter monitoring, chest radiography, thoracic computed tomography, magnetic resonance image and positron emission tomography. In general, sarcoidosis is treated with steroid compounds with good outcome, mainly when performed in the initial phases of the disease. Other cardiac manifestations, such as arrhythmias, atrioventricular block or heart failure, are managed similar to other cardiomyopathies.

Subacute and chronic hypersensitivity pneumonitis: histopathological patterns and survival.

BACKGROUND: In hypersensitivity pneumonitis (HP), survival can be predicted on the basis of the severity of fibrosis in surgical lung biopsy, but few data are available on the influence of clinical, functional, tomographic and histologic findings on prognosis. OBJECTIVES: To describe the impact on survival of clinical data, histological patterns, and HRCT findings in subacute/chronic HP. METHODS: A retrospective analysis of 103 patients diagnosed with HP submitted to surgical lung biopsy. Chronic HP was characterized by HRCT findings indicative of fibrosis (n=76). RESULTS: The most relevant exposures were to molds and birds. Lung biopsies revealed typical HP with granulomas in 46 patients, bronchiolocentric interstitial pneumonia in 27, and non-specific interstitial pneumonia (NSIP) in 16. By univariate analysis, several findings were predictors of mortality: older age, male sex, velcro crackles, higher FEV(1)/FVC ratio, lower oxygen saturation during exercise, and absence of mosaic pattern/air trapping and presence of fibrosis on HRCT. By multivariate analysis, remained significant: age (p=0.007), oxygen saturation during exercise (p=0.003), and mosaic pattern/air trapping on HRCT (p=0.004). Patients with NSIP had a greater survival than did those with typical histology and those with bronchiolocentric pneumonia (p=0.033). CONCLUSIONS: A wide range of histological features are found in HP. Typical findings are seen in 45% of cases. Other common patterns are NSIP and centriacinar lesions. Survival is better in patients with NSIP and worse in those with older age, desaturation during exercise, and absence of mosaic pattern/air trapping on HRCT.

Survival in idiopathic pulmonary fibrosis-cytotoxic agents compared to corticosteroids.

STUDY OBJECTIVE: To compare the survival of patients with IPF treated retrospectively with corticosteroids alone, to survival of patients treated with immunosuppressive and corticosteroids combined. DESIGN: Non-randomized retrospective cohort study. SETTING: Three tertiary centers in Brazil. PATIENTS: Eighty-two IPF patients were included. The diagnosis was confirmed by open lung biopsy in 48. Patients received either corticosteroids alone (group I) or cytotoxic agents in addition to corticosteroids (group II). MEASUREMENTS AND RESULTS: The primary end-point was mortality. Secondary outcome included longitudinal changes in FVC. Mean age was 66+/-8 years. FVC was 71+/-17% of predicted. There were 48 deaths during the study period (59%), 44 secondary to respiratory causes. From preliminary univariate analysis, for the group as a whole, worse survival was found to be associated with FVC% <70% of predicted (P=0.004), evidence of disease progression by follow-up FVC measurements (P=0.01), and pharmacologic treatment (P=0.014). Median survival was 25 months for the group I, and 45 months for the group II (Log-Rank=6.45, P=0.01). After adjusting for FVC > or =70% and<70% of predicted, there was evidence to indicate that survival was associated with recommended pharmacologic treatment only in patients with FVC> or =70% (Log Rank=6.84, P=0.009). CONCLUSIONS: The combination of immunosuppressive agents and prednisone results in better survival when compared to prednisone alone in patients with IPF. The benefit seems to occur only in patients with less severe disease, as reflected by FVC> or =70%.

[Bronchial provocation tests using methacholine, cycle ergometer exercise and free running in children with intermittent asthma]. / Testes de broncoprovocação com metacolina e com exercício em bicicleta e corrida livre em crianças com asma intermitente.

OBJECTIVE: To compare airway responsiveness to methacholine, cycle ergometer exercise and free running in children with intermittent asthma. METHODS: A randomized study was conducted with 30 children of both genders with intermittent asthma. Each child was submitted to challenge testing on three separate days, in random order: a) Methacholine challenge using a dosimeter; b) Exercise challenge testing -- free running along a 50-meter-long corridor; c) Dry-air exercise challenge on a cycle ergometer. Target heart rate during exercise was 80 to 90% of the maximum predicted value. Spirometry was performed 3, 6,10,15,20 and 30 minutes after exercise. Exercise-induced bronchospasm was defined as a decrease in FEV1 of > or = 10% in comparison to pretest values. RESULTS: Mean age was 11+/-3 years. FEV1 and FEV1/FVC ratios were normal and similar before all provocation tests. The maximum heart rate was 178+/-7 bpm during cycling and 181+/-6 bpm during the free running test (p > 0.05). Significant bronchospasm was observed with methacholine in 23 cases, after free running in 19 and after cycling in 14 children (p < 0.05, methacholine vs exercise tests). Taking all FEV1 measurements after exercise into account, the free running test resulted in greater exercise-induced bronchospasm in comparison with exercise made on a cycle ergometer (p = 0.003, chi2 = 8.948). There was a significant, but poor, correlation between the maximum percentage decrease in FEV1 after free running and cycling (r = 0.46, p < 0.01). CONCLUSIONS: Methacholine challenge identifies a greater number of asthmatics in comparison to exercise tests. When bronchial provocation test with methacholine is not available, free running should be the test of choice due to its simplicity and greater ability to induce bronchospasm.

Testes de broncoprovocação com metacolina e com exercício em bicicleta e corrida livre em crianças com asma intermitente / Bronchial provocation tests using methacholine, cycle ergometer exercise and free running in children with intermittent asthma

OBJETIVO: Comparar a responsividade de vias aéreas à metacolina e ao teste de exercício na bicicleta ergométrica e corrida livre em crianças com asma intermitente. MÉTODOS: Estudo randomizado. Trinta crianças de ambos os sexos com asma intermitente participaram do estudo. Cada teste foi realizado em 3 dias diferentes, através de randomização: a) broncoprovocação com metacolina, método do dosímetro; b) teste de exercício: corrida livre em um corredor de 50 m; c) teste de exercício: bicicleta ergométrica com ar seco. A freqüência cardíaca atingida foi 80 a 90 por cento da freqüência cardíaca máxima. A espirometria foi realizada aos 3, 6, 10, 15, 20 e 30 minutos após o exercício. Broncoespasmo induzido por exercício foi definido como a queda de volume expiratório forçado no primeiro segundo (VEF1) > 10 por cento em relação aos valores pré-teste. RESULTADOS: A média de idade foi 11±3 anos. O VEF1 e VEF1/CVF (capacidade vital forçada) foram normais e similares antes dos três testes de broncoprovocação. A freqüência cardíaca máxima foi de 178±7 bpm durante o exercício na bicicleta e 181±6 bpm na corrida livre (p > 0,05). Broncoespasmo significante foi visto em 23 crianças após o teste com metacolina, em 19 após a corrida livre e em 14 crianças após exercício em bicicleta (p < 0,05, metacolina versus testes de exercício). Levando-se em conta todas as medidas de VEF1 após o exercício, a corrida livre resultou em maior broncoespasmo em relação à bicicleta ergométrica (p = 0,003, chi2 = 8,948). Houve significante porém fraca correlação entre a queda máxima de VEF1 após a corrida livre e bicicleta (r = 0,46, p < 0,01). CONCLUSÕES: A broncoprovocação com metacolina identifica um maior número de asmáticos quando comparada aos testes de exercício. Quando a broncoprovocação com metacolina não estiver disponível, a corrida livre deve ser o teste de escolha, devido à sua simplicidade e maior capacidade de induzir broncoespasmo.

Clinical, radiographic and functional predictors of pulmonary gas exchange impairment at moderate exercise in patients with sarcoidosis.

BACKGROUND: Pulmonary gas exchange impairment (GEI) is a common consequence of intrathoracic sarcoidosis presenting with important therapeutic and prognostic implications. OBJECTIVE: To determine the role of clinical, radiographic and functional variables in predicting GEI during moderate exercise at the estimated lactate threshold (theta(L)) in patients with sarcoidosis. METHODS: Fifty-four outpatients (29 females) with biopsy-proven sarcoidosis had clinical evaluation (baseline dyspnea index), lung function tests and an incremental cardiopulmonary exercise test with theta(L) estimation. On a separate day, patients underwent a constant work rate test at theta(L) with assessment of arterial blood gas tensions. RESULTS: There was no evidence of GEI [DeltaP (A - a) O(2)/VO(2) >20 mm Hg.l. min(-1)] in patients with radiographic stages 0-I (n = 13). In the remaining 41 patients, GEI was associated with more extensive radiographic involvement and reduced diffusing capacity of the lung for carbon monoxide (DL(CO)), forced expiratory volume in 1 s, total lung capacity and forced vital capacity (% predicted;p < 0.05); baseline dyspnea index and resting arterial blood gas tensions, in contrast, were not significantly related to GEI. DL(CO) correlated best with GEI. The negative predictive value of DL(CO) >70% predicted (absent-to-mild impairment) was 91.3% (sensitivity = 81.8%) and the positive predictive value of DL(CO)