ABSTRACT
BACKGROUND: In real-world studies, the rate of discontinuation of nintedanib (NT) varies from 4% to 53%. Switching anti-fibrotic treatment in patients with idiopathic pulmonary fibrosis (IPF) has not been adequately investigated, and data on the tolerability and efficacy of changes in anti-fibrotic treatment is limited in clinical practice. OBJECTIVE: To identify factors associated with poor continuation of NT, efficacy and predictors of deterioration after switching from NT to pirfenidone (PFD) in patients with IPF. SUBJECTS AND METHODS: One hundred and seventy patients with IPF in whom NT was introduced between April 2017 and March 2022 were included to investigate NT continuation status and the effect of switching to PFD. RESULTS: A total of 123 patients (72.4%) continued NT for 1 year and had a significantly higher %forced vital capacity (FVC) at NT introduction than those who discontinued within 1 year (80.9% ± 16.3% vs. 71.9% ± 22.1%, P = 0.004). The determinant of poor NT continuation was the high GAP stage. On the other hand, 28 of 36 patients who discontinued NT because of disease progression switched to PFD. Consequently, FVC decline was suppressed before and after the change. The predictor of deterioration after the switch was a lower body mass index. CONCLUSIONS: In patients with IPF, early NT introduction increased continuation rates, and switching to PFD was effective when patients deteriorated despite initial NT treatment.
Subject(s)
Antifibrotic Agents , Idiopathic Pulmonary Fibrosis , Indoles , Pyridones , Humans , Idiopathic Pulmonary Fibrosis/drug therapy , Male , Pyridones/therapeutic use , Pyridones/adverse effects , Pyridones/administration & dosage , Female , Aged , Indoles/therapeutic use , Indoles/administration & dosage , Indoles/adverse effects , Vital Capacity/drug effects , Antifibrotic Agents/therapeutic use , Middle Aged , Treatment Outcome , Disease Progression , Drug Substitution , Aged, 80 and over , Retrospective StudiesABSTRACT
BACKGROUND: Chronic respiratory insufficiency from progressive muscle weakness causes morbidity and mortality in late-onset Pompe disease (LOPD). Previous Pompe Registry (NCT00231400) analyses for ≤ 5 years' alglucosidase alfa treatment showed a single linear time trend of stable forced vital capacity (FVC) % predicted. METHODS: To assess longer term Pompe Registry data, piecewise linear mixed model regression analyses estimated FVC% predicted trajectories in invasive-ventilator-free patients with LOPD aged ≥ 5 years. We estimated annual FVC change 0-6 months, > 6 months-5 years, and > 5-13 years from treatment initiation, adjusting for baseline age, sex, and non-invasive ventilation. FINDINGS: Among 485 patients (4612 FVC measurements; 8.3 years median follow-up), median ages at symptom onset, diagnosis, and alglucosidase alfa initiation were 34.3, 41.1, and 44.9 years, respectively. FVC% increased during the first 6 months' treatment (slope 1.83%/year; 95% confidence interval: 0.66, 3.01; P = 0.0023), then modestly declined -0.54%/year (-0.79, -0.30; P < 0.0001) during > 6 months-5 years, and -1.00%/year (-1.36, -0.63; P < 0.0001) during > 5-13 years. The latter two periods' slopes were not significantly different from each other (Pdifference = 0.0654) and were less steep than published natural history slopes (-1% to -4.6%/year). Estimated individual slopes were ≥ 0%/year in 96.1%, 30.3%, and 13.2% of patients during the 0-6 month, > 6 month-5 year, and > 5-13 year periods, respectively. CONCLUSION: These real-world data indicate an alglucosidase alfa benefit on FVC trajectory that persists at least 13 years compared with published natural history data. Nevertheless, unmet need remains since most individuals demonstrate lung function decline 5 years after initiating treatment. Whether altered FVC trajectory impacts respiratory failure incidence remains undetermined. TRIAL REGISTRATION: This study was registered (NCT00231400) on ClinicalTrials.gov on September 30, 2005, retrospectively registered.
Subject(s)
Glycogen Storage Disease Type II , Registries , alpha-Glucosidases , Humans , Glycogen Storage Disease Type II/drug therapy , Glycogen Storage Disease Type II/physiopathology , Male , Female , alpha-Glucosidases/therapeutic use , Adult , Vital Capacity/drug effects , Vital Capacity/physiology , Middle Aged , Enzyme Replacement Therapy/methods , Young Adult , Adolescent , Child , Follow-Up Studies , Child, PreschoolABSTRACT
Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain largely unexplored. Herein, a longitudinal panel study was conducted in Jinan, Shandong Province, China, involving 76 healthy older adults monitored over a span of five months repetitively. We systematically evaluated personal exposure to a diverse range of airborne organic pollutants using a wearable passive sampler and their effects on lung function. Participants' pulmonary function indicators were assessed, complemented by comprehensive multi-omics analyses of blood and urine samples. Leveraging the power of interaction analysis, causal inference test (CIT), and integrative pathway analysis (IPA), we explored intricate relationships between specific organic pollutants, biomolecules, and lung function deterioration, elucidating the biological mechanisms underpinning the adverse impacts of these pollutants. We observed that bis (2-chloro-1-methylethyl) ether (BCIE) was significantly associated with negative changes in the forced vital capacity (FVC), with glycerolipids mitigating this adverse effect. Additionally, 31 canonical pathways [e.g., high mobility group box 1 (HMGB1) signaling, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, epithelial mesenchymal transition, and heme and nicotinamide adenine dinucleotide (NAD) biosynthesis] were identified as potential mechanisms. These findings may hold significant implications for developing effective strategies to prevent and mitigate respiratory health risks arising from exposure to such airborne pollutants. However, due to certain limitations of the study, our results should be interpreted with caution.
Subject(s)
Air Pollutants , Humans , Aged , Air Pollutants/analysis , Air Pollutants/toxicity , Male , Female , China , Longitudinal Studies , Middle Aged , Lung/drug effects , Environmental Exposure/adverse effects , Respiratory Function Tests , Vital Capacity/drug effectsABSTRACT
BACKGROUND: The treatment response to corticosteroids in patients with sarcoidosis is highly variable. CD4+ T cells are central in sarcoid pathogenesis and their phenotype in peripheral blood (PB) associates with disease course. We hypothesized that the phenotype of circulating T cells in patients with sarcoidosis may correlate with the response to prednisone treatment. Therefore, we aimed to correlate frequencies and phenotypes of circulating T cells at baseline with the pulmonary function response at 3 and 12 months during prednisone treatment in patients with pulmonary sarcoidosis. METHODS: We used multi-color flow cytometry to quantify activation marker expression on PB T cell populations in 22 treatment-naïve patients and 21 healthy controls (HCs). Pulmonary function tests at baseline, 3 and 12 months were used to measure treatment effect. RESULTS: Patients with sarcoidosis showed an absolute forced vital capacity (FVC) increase of 14.2% predicted (± 10.6, p < 0.0001) between baseline and 3 months. Good response to prednisone (defined as absolute FVC increase of ≥ 10% predicted) was observed in 12 patients. CD4+ memory T cells and regulatory T cells from patients with sarcoidosis displayed an aberrant phenotype at baseline, compared to HCs. Good responders at 3 months had significantly increased baseline proportions of PD-1+CD4+ memory T cells and PD-1+ regulatory T cells, compared to poor responders and HCs. Moreover, decreased fractions of CD25+ cells and increased fractions of PD-1+ cells within the CD4+ memory T cell population correlated with ≥ 10% FVC increase at 12 months. During treatment, the aberrantly activated phenotype of memory and regulatory T cells reversed. CONCLUSIONS: Increased proportions of circulating PD-1+CD4+ memory T cells and PD-1+ regulatory T cells and decreased proportions of CD25+CD4+ memory T cells associate with good FVC response to prednisone in pulmonary sarcoidosis, representing promising new blood biomarkers for prednisone efficacy. TRIAL REGISTRATION: NL44805.078.13.
Subject(s)
Prednisone , Programmed Cell Death 1 Receptor , Sarcoidosis, Pulmonary , T-Lymphocytes, Regulatory , Humans , Male , Sarcoidosis, Pulmonary/drug therapy , Sarcoidosis, Pulmonary/blood , Sarcoidosis, Pulmonary/immunology , Sarcoidosis, Pulmonary/diagnosis , Female , Middle Aged , Prednisone/therapeutic use , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Adult , Treatment Outcome , Memory T Cells/drug effects , Memory T Cells/immunology , Memory T Cells/metabolism , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Glucocorticoids/therapeutic use , Vital Capacity/drug effects , AgedSubject(s)
Adaptor Proteins, Signal Transducing , Antifibrotic Agents , Apoptosis Regulatory Proteins , Scleroderma, Systemic , Humans , Scleroderma, Systemic/drug therapy , Scleroderma, Systemic/blood , Female , Apoptosis Regulatory Proteins/metabolism , Middle Aged , Male , Vital Capacity/drug effects , Antifibrotic Agents/pharmacology , Antifibrotic Agents/therapeutic use , Adult , Fibrosis , AgedABSTRACT
BACKGROUND: Elexacaftor in combination with Tezacaftor and Ivacaftor (ETI) became licensed in the United Kingdom in early 2022 for children aged 6-11 years with cystic fibrosis (CF) and an eligible mutation. Many in this age group have excellent prior lung health making quantitative measurement of benefit challenging. Clinical trials purport that lung clearance index (LCI2.5) measurement is most suitable for this purpose. OBJECTIVES: This study aimed to understand the clinical utility of LCI2.5 in detecting change after commencing ETI in the real world. PATIENT SELECTION/METHODS: Baseline anthropometric data were collected along with spirometry (forced expiratory volume in 1 s [FEV1], forced vital capacityFV and LCI2.5 measures in children aged 6-11 years with CF before starting ETI. Measures were repeated after a mean (range) of 8.2 (7-14) months of ETI treatment. The primary endpoint was a change in LCI2.5, with secondary endpoints including change in FEV1 and change in body mass index (BMI) also reported. RESULTS: Twelve children were studied (seven male, mean age 9.5 years at baseline). Our study population had a mean (SD) LCI2.5 of 7.01 (1.14) and FEV1 of 96 (13) %predicted at baseline. Mean (95% confidence interval) changes in LCI2.5 [-0.7 (-1.4, 0), p = .06] and BMI [+0.7 (+0.1, +1.3), p = .03] were observed, along with changes in FEV1 of +3.1 (-1.9, +8.1) %predicted. CONCLUSIONS: Real-world changes in LCI2.5 (-0.7) are different to those reported in clinical trials (-2.29). Lower baseline LCI2.5 as a result of prior modulator exposure, high baseline lung health, and new LCI2.5 software analyses all contribute to lower LCI2.5 values being recorded in the real world of children with CF.
Subject(s)
Aminophenols , Benzodioxoles , Cystic Fibrosis , Drug Combinations , Indoles , Pyrrolidines , Quinolones , Humans , Cystic Fibrosis/drug therapy , Cystic Fibrosis/physiopathology , Child , Male , Female , Aminophenols/therapeutic use , Quinolones/therapeutic use , Indoles/therapeutic use , Forced Expiratory Volume/drug effects , Benzodioxoles/therapeutic use , Pyridines/therapeutic use , Pyrazoles/therapeutic use , Lung/physiopathology , Lung/drug effects , Pyrroles/therapeutic use , Vital Capacity/drug effects , Spirometry , Chloride Channel Agonists/therapeutic useABSTRACT
Rationale: A phase II trial reported clinical benefit over 28 weeks in patients with idiopathic pulmonary fibrosis (IPF) who received zinpentraxin alfa. Objectives: To investigate the efficacy and safety of zinpentraxin alfa in patients with IPF in a phase III trial. Methods: This 52-week phase III, double-blind, placebo-controlled, pivotal trial was conducted at 275 sites in 29 countries. Patients with IPF were randomized 1:1 to intravenous placebo or zinpentraxin alfa 10 mg/kg every 4 weeks. The primary endpoint was absolute change from baseline to Week 52 in FVC. Secondary endpoints included absolute change from baseline to Week 52 in percent predicted FVC and 6-minute walk distance. Safety was monitored via adverse events. Post hoc analysis of the phase II and phase III data explored changes in FVC and their impact on the efficacy results. Measurements and Main Results: Of 664 randomized patients, 333 were assigned to placebo and 331 to zinpentraxin alfa. Four of the 664 randomized patients were never administered study drug. The trial was terminated early after a prespecified futility analysis that demonstrated no treatment benefit of zinpentraxin alfa over placebo. In the final analysis, absolute change from baseline to Week 52 in FVC was similar between placebo and zinpentraxin alfa (-214.89 ml and -235.72 ml; P = 0.5420); there were no apparent treatment effects on secondary endpoints. Overall, 72.3% and 74.6% of patients receiving placebo and zinpentraxin alfa, respectively, experienced one or more adverse events. Post hoc analysis revealed that extreme FVC decline in two placebo-treated patients resulted in the clinical benefit of zinpentraxin alfa reported by phase II. Conclusions: Zinpentraxin alfa treatment did not benefit patients with IPF over placebo. Learnings from this program may help improve decision making around trials in IPF. Clinical trial registered with www.clinicaltrials.gov (NCT04552899).
Subject(s)
Idiopathic Pulmonary Fibrosis , Humans , Female , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/physiopathology , Male , Double-Blind Method , Aged , Middle Aged , Treatment Outcome , Vital Capacity/drug effectsABSTRACT
BACKGROUND: Mine workers face various health risks from occupational hazards, notably dust-related pulmonary dysfunction. This dysfunction is also attributed to diverse risk factors and health conditions. Despite the variety of underlying mechanisms, conflicting evidence persists regarding hypertension as a potential risk factor for such dysfunction. OBJECTIVE: To determine the predictors of pulmonary dysfunction vis-à-vis the hypertension status of mine workers. METHODS: We conducted a cross-sectional study among 444 mine workers from ten open-cast mines in Gujarat state (western part of India) from November 2020 to February 2022. We collected data on demographics, occupation, addiction, and comorbidities, including measurements like anthropometry, blood pressure, blood sugar, haemoglobin, and lipid levels. Hypertension was confirmed based on self-reported history and/or onsite blood pressure measurement, while pulmonary functions were assessed using a spirometer (expressed as forced expiratory volume in the first second FEV1 and forced vital capacity FVC). Multiple linear regression analysis was performed to determine the significant predictor of FEV1 or FVC vis-à-vis the hypertension status after adjusting for confounding variables. In addition, we assessed the effect of anti-hypertensive medications on pulmonary dysfunction. RESULTS: A total of 41% (95% CI: 36-45%) of mine workers were suffering from hypertension. On multiple linear regression, only being a male and work experience duration were the significant predictors of FEV1 [0.900 (0.475-1.092), p=<0.001; -0.029 (-0.034 - -0.021, p=<0.001] and FVC [1.088 (0.771-1.404), p=<0.001; -0.031 (-0.038 - -0.024, pâ=â0.001] respectively. While unadjusted analysis indicated hypertension led to FEV1 and FVC reduction, this effect lost significance after adjusting for confounders. Nevertheless, subgroup analysis revealed those on antihypertensive medications had reductions in FEV1 and FVC by -0.263 (95% CI: -0.449 - -0.078, pâ=â0.006) L and -0.271 (95% CI: -0.476 - -0.067, pâ=â0.009) L respectively. CONCLUSION: In our study among mine workers, alterations in lung function (FEV1 and FVC) on spirometry were predicted by gender and duration of work experience, while hypertension did not serve as a predictor. It is noteworthy that antihypertensive drugs were found to reduce lung functions on spirometry, highlighting the need for further research.
Subject(s)
Antihypertensive Agents , Hypertension , Humans , Cross-Sectional Studies , Male , India/epidemiology , Female , Adult , Hypertension/epidemiology , Hypertension/drug therapy , Antihypertensive Agents/adverse effects , Antihypertensive Agents/therapeutic use , Middle Aged , Miners/statistics & numerical data , Mining/statistics & numerical data , Risk Factors , Lung Diseases/epidemiology , Lung Diseases/physiopathology , Lung Diseases/chemically induced , Lung Diseases/etiology , Vital Capacity/drug effects , Occupational Exposure/adverse effects , Occupational Exposure/statistics & numerical data , Respiratory Function TestsABSTRACT
RESUMO Objetivo Ensaios clínicos mostraram que 150 mg de Nintedanibe duas vezes ao dia reduzem a progressão da doença em pacientes com Fibrose Pulmonar Idiopática (FPI), com um perfil de efeitos adversos que é controlável para a maioria dos pacientes. Antes da aprovação do Nintedanibe como tratamento para a FPI no Brasil, um Programa de Acesso Expandido (PEA) foi iniciado para fornecer acesso precoce ao tratamento e avaliar a segurança e a tolerância do Nintedanibe para este grupo de pacientes. Métodos Foram elegíveis para participar da PEA pacientes com diagnóstico de FPI nos últimos 5 anos, com capacidade vital forçada (CVF) ≥ 50% do previsto e capacidade de difusão dos pulmões para monóxido de carbono (DLco) 30%-79% do previsto. Os pacientes receberam Nintedanibe 150 mg, 2 vezes ao dia (bid). As avaliações de segurança incluíram eventos adversos que levaram à suspensão permanente do Nintedanibe e eventos adversos graves. Resultados O PEA envolveu 57 pacientes em 8 centros. A maioria dos pacientes era do sexo masculino (77,2%) e brancos (87,7%). No início do estudo, a média de idade foi de 70,7 (7,5) anos e a CVF foi de 70,7 (12,5%) do previsto. A média de exposição ao Nintedanibe foi de 14,4 (6,2) meses; a exposição máxima foi de 22,0 meses. Os eventos adversos frequentemente relatados pelo pesquisador como relacionados ao tratamento com Nintedanibe foram diarreia (45 pacientes, 78,9%) e náusea (25 pacientes, 43,9%). Os eventos adversos levaram à suspensão permanente do Nintedanibe em 16 pacientes (28,1%) que passaram por um evento adverso grave. Conclusões No PEA brasileiro, o Nintedanibe apresentou um perfil aceitável de segurança e tolerância em pacientes com FPI, condizendo com dados de ensaios clínicos.
ABSTRACT Objective Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. Methods Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. Results The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. Conclusion In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Idiopathic Pulmonary Fibrosis/drug therapy , Indoles/administration & dosage , Aspartate Aminotransferases/analysis , Time Factors , Vomiting/chemically induced , Algorithms , Brazil , Vital Capacity/drug effects , Reproducibility of Results , Treatment Outcome , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Diarrhea/chemically induced , Drug Tolerance , Chemical and Drug Induced Liver Injury/etiology , Transaminases/analysis , Indoles/adverse effects , Nausea/chemically inducedABSTRACT
Few studies evaluate the amount of particulate matter less than 2.5 mm in diameter (PM2.5) in relation to a change in lung function among adults in a population. The aim of this study was to assess the association of coal as a domestic energy source to pulmonary function in an adult population in inner-city areas of Zunyi city in China where coal use is common. In a cross-sectional study of 104 households, pulmonary function measurements were assessed and compared in 110 coal users and 121 non-coal users (≥18 years old) who were all nonsmokers. Several sociodemographic factors were assessed by questionnaire, and ventilatory function measurements including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), the FEV1/FVC ratio, and peak expiratory flow rate (PEFR) were compared between the 2 groups. The amount of PM2.5 was also measured in all residences. There was a significant increase in the relative concentration of PM2.5 in the indoor kitchens and living rooms of the coal-exposed group compared to the non-coal-exposed group. In multivariate analysis, current exposure to coal smoke was associated with a 31.7% decrease in FVC, a 42.0% decrease in FEV1, a 7.46% decrease in the FEV1/FVC ratio, and a 23.1% decrease in PEFR in adult residents. The slope of lung function decrease for Chinese adults is approximately a 2-L decrease in FVC, a 3-L decrease in FEV1, and an 8 L/s decrease in PEFR per count per minute of PM2.5 exposure. These results demonstrate the harmful effects of indoor air pollution from coal smoke on the lung function of adult residents and emphasize the need for public health efforts to decrease exposure to coal smoke.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Air Pollution, Indoor/adverse effects , Coal/toxicity , Lung/physiology , Particulate Matter/toxicity , China , Cities , Cross-Sectional Studies , Forced Expiratory Volume/drug effects , Housing , Particulate Matter/analysis , Respiratory Function Tests , Respiratory Tract Infections/etiology , Socioeconomic Factors , Smoke/adverse effects , Tobacco Smoke Pollution/adverse effects , Vital Capacity/drug effectsABSTRACT
OBJECTIVE: To investigate the modulatory effects that dynamic hyperinflation (DH), defined as a reduction in inspiratory capacity (IC), has on exercise tolerance after bronchodilator in patients with COPD. METHODS: An experimental, randomized study involving 30 COPD patients without severe hypoxemia. At baseline, the patients underwent clinical assessment, spirometry, and incremental cardiopulmonary exercise testing (CPET). On two subsequent visits, the patients were randomized to receive a combination of inhaled fenoterol/ipratropium or placebo. All patients then underwent spirometry and submaximal CPET at constant speed up to the limit of tolerance (Tlim). The patients who showed ΔIC(peak-rest) < 0 were considered to present with DH (DH+). RESULTS: In this sample, 21 patients (70%) had DH. The DH+ patients had higher airflow obstruction and lower Tlim than did the patients without DH (DH-). Despite equivalent improvement in FEV1 after bronchodilator, the DH- group showed higher ΔIC(bronchodilator-placebo) at rest in relation to the DH+ group (p < 0.05). However, this was not found in relation to ΔIC at peak exercise between DH+ and DH- groups (0.19 ± 0.17 L vs. 0.17 ± 0.15 L, p > 0.05). In addition, both groups showed similar improvements in Tlim after bronchodilator (median [interquartile range]: 22% [3-60%] vs. 10% [3-53%]; p > 0.05). CONCLUSIONS: Improvement in TLim was associated with an increase in IC at rest after bronchodilator in HD- patients with COPD. However, even without that improvement, COPD patients can present with greater exercise tolerance after bronchodilator provided that they develop DH during exercise. .
OBJETIVO: Investigar os efeitos moduladores da hiperinsuflação dinâmica (HD), definida pela redução da capacidade inspiratória (CI), na tolerância ao exercício após broncodilatador em pacientes com DPOC. MÉTODOS: Estudo experimental e randomizado com 30 pacientes com DPOC sem hipoxemia grave. Na visita inicial, os pacientes realizaram avaliação clínica, espirometria e teste de exercício cardiopulmonar (TECP) incremental. Em duas visitas subsequentes, os pacientes foram randomizados para receber uma combinação de fenoterol/ipratrópio ou placebo e, em seguida, realizaram espirometria e TECP com velocidade constante até o limite da tolerância (Tlim). Os pacientes com ΔCI(pico-repouso) < 0 foram considerados com HD (HD+). RESULTADOS: Nesta amostra, 21 pacientes (70%) apresentaram HD. Os pacientes HD+ apresentaram maior obstrução ao fluxo aéreo e menor Tlim do que os pacientes sem HD (HD-). Apesar de ganhos equivalentes de VEF1 após broncodilatador, o grupo HD- apresentou maior ΔCI(broncodilatador-placebo) em repouso em relação ao grupo HD+ (p < 0,05). Entretanto, isso não ocorreu com a ΔCI no pico do exercício entre os grupos HD+ e HD- (0,19 ± 0,17 L vs. 0,17 ± 0,15 L; p > 0,05). Similarmente, ambos os grupos apresentaram melhoras equivalentes do Tlim após broncodilatador (mediana [intervalo interquartílico]: 22% [3-60%] e 10% [3-53%]; p > 0,05). CONCLUSÕES: A melhora da CI em repouso após broncodilatador associou-se com ganho de tolerância ao esforço mesmo nos pacientes com DPOC que não apresentem HD. Por outro lado, pacientes sem melhora da CI em repouso ainda podem obter beneficio funcional com o broncodilatador desde que apresentem HD no exercício. .
Subject(s)
Adult , Humans , Bronchodilator Agents/therapeutic use , Exercise Test/methods , Exercise Tolerance/drug effects , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/physiopathology , Forced Expiratory Volume/drug effects , Inspiratory Capacity/drug effects , Lung/physiopathology , Placebos , Spirometry , Vital Capacity/drug effectsABSTRACT
OBJETIVO: Avaliar o bloqueio da metaloproteinase da matriz (MMP)-2 e da MMP-9 e a variação do VEF1 em pacientes com linfangioleiomiomatose (LAM) após o uso de doxiciclina, um conhecido inibidor de MMP, durante 12 meses. MÉTODOS: Ensaio clínico aberto de braço único no qual as pacientes com diagnóstico de LAM receberam doxiciclina (100 mg/dia) durante 12 meses. Elas foram submetidas a prova de função pulmonar completa, teste de caminhada de seis minutos, avaliação da qualidade de vida e coleta de amostras séricas e urinárias para dosagem de MMP-2, MMP-9 e VEGF-D antes do início do tratamento com doxiciclina e após 6 e 12 meses de tratamento. RESULTADOS: Trinta e uma pacientes com LAM receberam doxiciclina durante 12 meses. Embora tenha havido um bloqueio efetivo da MMP-9 urinária e da MMP-2 sérica após o tratamento, os níveis séricos de MMP-9 e VEGF-D permaneceram estáveis. Com base na resposta à doxiciclina (determinada pela variação do VEF1), as pacientes foram divididas em dois grupos: respondedoras (doxi-R; n = 13) e não respondedoras (doxi-NR; n = 18). As pacientes com alterações espirométricas leves apresentaram melhor resposta à doxiciclina. Os efeitos colaterais mais comuns foram epigastralgia, náusea e diarreia, todos de leve intensidade. CONCLUSÕES: Em pacientes com LAM, o tratamento com doxiciclina resulta em um bloqueio eficaz das MMP, além de melhorar a função pulmonar e a qualidade de vida daqueles com doença menos grave. No entanto, esses benefícios não parecem estar relacionados ao bloqueio das MMP, o que sugere um mecanismo de ação diferente. (Registro Brasileiro de Ensaios Clínicos - ReBEC; número de identificação RBR-6g8yz9 [http://www.ensaiosclinicos.gov.br]).
OBJECTIVE: To assess blockade of matrix metalloproteinase (MMP)-2 and MMP-9, as well as the variation in FEV1, in patients with lymphangioleiomyomatosis (LAM) treated with doxycycline (a known MMP inhibitor) for 12 months. METHODS: An open-label, single-arm, interventional clinical trial in which LAM patients received doxycycline (100 mg/day) for 12 months. Patients underwent full pulmonary function testing, a six-minute walk test, and quality of life assessment, as well as blood and urine sampling for quantification of MMP-2, MMP-9, and VEGF-D levels-at baseline, as well as at 6 and 12 months after the initiation of doxycycline. RESULTS: Thirty-one LAM patients received doxycycline for 12 months. Although there was effective blockade of urinary MMP-9 and serum MMP-2 after treatment, there were no significant differences between pre- and post-doxycycline serum levels of MMP-9 and VEGF-D. On the basis of their response to doxycycline (as determined by the variation in FEV1), the patients were divided into two groups: the doxycycline-responder (doxy-R) group (n = 13); and the doxycycline-nonresponder (doxy-NR) group (n = 18). The patients with mild spirometric abnormalities responded better to doxycycline. The most common side effects were mild epigastric pain, nausea, and diarrhea. CONCLUSIONS: In patients with LAM, doxycycline treatment results in effective MMP blockade, as well as in improved lung function and quality of life in those with less severe disease. However, these benefits do not seem to be related to the MMP blockade, raising the hypothesis that there is a different mechanism of action. (Brazilian Registry of Clinical Trials - ReBEC; identification number RBR-6g8yz9 [http://www.ensaiosclinicos.gov.br]).
Subject(s)
Adult , Female , Humans , Doxycycline/therapeutic use , Lymphangioleiomyomatosis/drug therapy , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase Inhibitors/therapeutic use , /metabolism , Vital Capacity/drug effects , Biomarkers/blood , Biomarkers/urine , Doxycycline/adverse effects , Exercise Test , Lymphangioleiomyomatosis/metabolism , Matrix Metalloproteinase Inhibitors/adverse effects , Quality of Life , ROC Curve , Statistics, Nonparametric , Vascular Endothelial Growth Factor A/metabolism , WalkingABSTRACT
OBJETIVO: Estabelecer os limites superiores para mudanças em VEF1, capacidade vital lenta (CVL), CVF e capacidade inspiratória (CI) após o uso de placebo em pacientes com obstrução ao fluxo aéreo. MÉTODOS: Cento e dois adultos com obstrução ao fluxo aéreo (VEF1 = 62 ± 19% do previsto) foram incluídos neste estudo. Todos os participantes realizaram manobras de CVL e CVF antes e depois do uso de spray de placebo. As mudanças em VEF1, CVL, CVF e CI foram expressas em valores absolutos, porcentagem de variação em relação aos valores basais e porcentagem dos valores previstos, e foram calculados os IC95% e os percentis 95. A análise fatorial foi realizada a fim de determinar como essas alterações se agrupavam. RESULTADOS: Considerando os IC95% e percentis 95 e após o arredondamento dos valores, obtivemos os seguintes limites superiores para resposta significante: VEF1 = 0,20 L, CVF = 0,20 L, CVL = 0,25 L e CI = 0,30 L (em valores absolutos); VEF1 = 12%, CVF = 7%, CVL = 10% e CI = 15% (em porcentagem de variação em relação aos valores basais) e VEF1 = 7%, CVF = 6%, CVL = 7% e CI = 12% (em porcentagem dos valores previstos). CONCLUSÕES: Em pacientes com obstrução ao fluxo aéreo, a CI apresenta maior variabilidade do que a CVF e a CVL. Para a CI, valores maiores que 0,30 L e 15% de variação em relação ao valor basal devem ser considerados significantes. Para CVF, valores maiores que 0,20L e 7% de variação em relação ao valor basal são significantes. Alternativamente, alterações de mais de 0,20 L e 7% do previsto no VEF1 e na CVF devem ser consideradas significantes. Na análise fatorial, os parâmetros espirométricos se agruparam em três dimensões, expressando mudanças no fluxo, volume e hiperinsuflação dinâmica.
OBJECTIVE: To establish the upper limits for changes in FEV1, slow vital capacity (SVC), FVC, and inspiratory capacity (IC) after placebo administration in patients with airflow obstruction. METHODS: One hundred and two adults with airflow obstruction (FEV1 = 62 ± 19% of predicted) were included in the study. All of the participants performed SVC and FVC maneuvers before and after the administration of placebo spray. The changes in FEV1, SVC, FVC, and IC were expressed as absolute values, percentage of change from baseline values, and percentage of predicted values, 95% CIs and 95th percentiles being calculated. Factor analysis was performed in order to determine how those changes clustered. RESULTS: Considering the 95% CIs and 95th percentiles and after rounding the values, we found that the upper limits for a significant response were as follows: FEV1 = 0.20 L, FVC = 0.20 L, SVC = 0.25 L, and IC = 0.30 L (expressed as absolute values); FEV1 = 12%, FVC = 7%, SVC = 10%, and IC = 15% (expressed as percentage of change from baseline values); and FEV1 = 7%, FVC = 6%, SVC = 7%, and IC = 12% (expressed as percentage of predicted values). CONCLUSIONS: In patients with airflow obstruction, IC varies more widely than do FVC and SVC. For IC, values greater than 0.30 L and 15% of change from the baseline value can be considered significant. For FVC, values greater than 0.20 L and 7% of change from the baseline value are significant. Alternatively, changes exceeding 0.20 L and 7% of the predicted value can be considered significant for FEV1 and FVC. On factor analysis, spirometric parameters clustered into three dimensions, expressing changes in flows, volumes, and dynamic hyperinflation.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Bronchodilator Agents/administration & dosage , Lung Diseases, Obstructive/drug therapy , Placebos/pharmacology , Vital Capacity/drug effects , Bronchodilator Agents/therapeutic use , Factor Analysis, Statistical , Forced Expiratory Volume/drug effects , Inspiratory Capacity/drug effects , Lung Diseases, Obstructive/physiopathology , Nasal Sprays , Placebos/administration & dosage , Spirometry , Statistics, NonparametricABSTRACT
To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) with oral solubilized formula in amyotrophic lateral sclerosis (ALS) patients, patients with probable or definite ALS were randomized to receive oral solubilized UDCA (3.5 g/140 mL/day) or placebo for 3 months after a run-in period of 1 month and switched to receive the other treatment for 3 months after a wash-out period of 1 month. The primary outcome was the rate of progression, assessed by the Appel ALS rating scale (AALSRS), and the secondary outcomes were the revised ALS functional rating scale (ALSFRS-R) and forced vital capacity (FVC). Fifty-three patients completed either the first or second period of study with only 16 of 63 enrolled patients given both treatments sequentially. The slope of AALSRS was 1.17 points/month lower while the patients were treated with UDCA than with placebo (95% CI for difference 0.08-2.26, P = 0.037), whereas the slopes of ALSFRS-R and FVC did not show significant differences between treatments. Gastrointestinal adverse events were more common with UDCA (P < 0.05). Oral solubilized UDCA seems to be tolerable in ALS patients, but we could not make firm conclusion regarding its efficacy, particularly due to the high attrition rate in this cross-over trial.
Subject(s)
Female , Humans , Male , Middle Aged , Administration, Oral , Amyotrophic Lateral Sclerosis/drug therapy , Cholagogues and Choleretics/pharmacology , Cross-Over Studies , Double-Blind Method , Placebo Effect , Severity of Illness Index , Ursodeoxycholic Acid/pharmacology , Vital Capacity/drug effectsABSTRACT
Nas células musculares lisas atípicas características da linfangioleiomiomatose (LAM) encontram-se receptores de estrogênio e progesterona, de modo que o tratamento anti-hormonal pode ser considerado uma opção, mas ainda com resultados controversos. O objetivo deste trabalho foi avaliar retrospectivamente parâmetros hormonais e espirométricos em nove mulheres com LAM após o tratamento com goserelina por um ano. Houve um aumento médio de 80 mL e 130 mL, respectivamente, em VEF1 e CVF, assim como bloqueio hormonal efetivo. Ainda não se pode excluir um potencial efeito favorável da utilização de análogos de hormônio liberador de gonadotrofina em pacientes com LAM, reforçando a necessidade de ensaios randomizados.
In the atypical smooth muscle cells that are characteristic of lymphangioleiomyomatosis (LAM), there are estrogen and progesterone receptors. Therefore, anti-hormonal therapy, despite having produced controversial results, can be considered a treatment option. The objective of this retrospective study was to evaluate hormonal and spirometric data for nine women with LAM after one year of treatment with goserelin. The mean increase in FEV1 and FVC was 80 mL and 130 mL, respectively. There was effective blockage of the hormonal axis. It is still not possible to exclude a potential beneficial effect of the use of gonadotropin-releasing hormone analogues in LAM patients, which underscores the need for randomized trials.
Subject(s)
Adult , Female , Humans , Middle Aged , Young Adult , Antineoplastic Agents, Hormonal/therapeutic use , Goserelin/therapeutic use , Lymphangioleiomyomatosis/physiopathology , Vital Capacity/drug effects , Hormones/metabolism , Lymphangioleiomyomatosis/drug therapy , Retrospective Studies , Statistics, NonparametricABSTRACT
JUSTIFICATIVA E OBJETIVOS: A via interescalênica é um dos acessos mais comumente utilizados no bloqueio do plexo braquial. Todavia, tem-se demonstrado associação dessa técnica com o bloqueio do nervo frênico ipsilateral. A disfunção diafragmática daí resultante provoca alterações na mecânica pulmonar, potencialmente deletérias em pacientes com limitação da reserva ventilatória. O objetivo do estudo foi avaliar a repercussão do bloqueio interescalênico sobre a função pulmonar por meio da medida da capacidade vital forçada (CVF). MÉTODO: Estudo duplamente encoberto com 30 pacientes, estado físico I ou II (ASA), distribuídos aleatoriamente em dois grupos de15. Foi administrada solução a 0,5 por cento de ropivacaína (Grupo Ropi) ou bupivacaína a 0,5 por cento com epinefrina (Grupo Bupi). O bloqueio foi realizado utilizando estimulador de nervo periférico e sendo injetados 30 mL de anestésico local. Quatro espirometrias foram realizadas em cada paciente: antes do bloqueio, 30 minutos, 4 e 6 horas após. Os pacientes não receberam sedação. RESULTADOS: Um paciente do Grupo Ropi e três pacientes do Grupo Bupi foram excluídos do estudo por falha de bloqueio. A redução da CVF no Grupo Ropi foi máxima aos 30 minutos (25,1 por cento) e a partir de então houve tendência progressiva à recuperação. Já com bupivacaína, a redução da CVF pareceu ser menos acentuada nos diversos momentos estudados; observou-se redução adicional entre 30 minutos (15,8 por cento) e 4 horas (17,3 por cento), sendo esta sem diferença estatística. A partir de 4 horas, notou-se tendência à recuperação. Em ambos os grupos, após 6 horas de bloqueio a CVF encontra-se ainda abaixo dos valores prévios. CONCLUSÕES: O bloqueio interescalênico reduz a CVF na maioria dos casos; as alterações foram mais acentuadas no Grupo Ropivacaína.
BACKGROUND AND OBJECTIVES: The interscalene is one of the most common approaches used in brachial plexus block. However, the association of this approach with the ipsilateral blockade of the phrenic nerve has been demonstrated. The resulting diaphragmatic dysfunction causes changes in lung mechanics, which can be potentially deleterious in patients with limited respiratory reserve. The objective of the present study was to evaluate the repercussion of interscalene brachial plexus block on pulmonary function by measuring forced vital capacity (FVC). METHODS: This is a double-blind study with 30 patients, physical status ASA I or II, randomly separated into two groups of 15 patients each; 0.5 percent ropivacaine (Ropi Group) or 0.5 percent bupivacaine with epinephrine (Bupi Group) was administered. A peripheral nerve stimulator was used, and 30 mL of the local anesthetic were administered. Four spirometries were done in each patient: before the blockade, 30 minutes, four hours, and six hours after the blockade. Patients were not sedated. RESULTS: One patient in the Ropi Group and three patients in the Bupi Group were excluded from the study due to failure of the blockade. The Ropi Group showed maximal FVC reduction at 30 minutes (25.1 percent), with a tendency for recovery from this point on. With bupivacaine, the reduction in FVC was less important at the different study moments; an additional reduction was observed between 30 (15.8 percent) and four hours (17.3 percent), but it was not statistically significant. A tendency for recovery was observed from four hours on. In both groups, the FVC six hours after the blockade was still below baseline levels. CONCLUSIONS: Interscalene block reduces FVC in most cases. Changes were more pronounced in the Ropivacaine group.
JUSTIFICATIVA Y OBJETIVOS: La vía interescalénica es uno de los accesos más a menudo utilizados en el bloqueo del plexo braquial. Sin embargo, se ha demostrado una asociación de esa técnica con el bloqueo del nervio frénico ipsilateral. La disfunción diafragmática de resultas de esa asociación, provoca alteraciones en la mecánica pulmonar, potencialmente perjudiciales en pacientes con una limitación de la reserva ventilatoria. El objetivo del estudio fue evaluar la repercusión del bloqueo interescalénico sobre la función pulmonar por medio de la medida de la capacidad vital forzada (CVF). MÉTODO: Estudio doble ciego, con 30 pacientes, estado físico I o II (ASA), distribuidos aleatoriamente en dos grupos de 15. Se administró solución a 0,5 por ciento de ropivacaína (Grupo Ropi) o bupivacaína a 0,5 por ciento con epinefrina (Grupo Bupi). El bloqueo fue realizado utilizando estimulador de nervio periférico e inyectando 30 mL de anestésico local. Cuatro espirometrías se hicieron en cada paciente: antes del bloqueo, 30 minutos, 4 y 6 horas después. Los pacientes no recibieron sedación. RESULTADOS: Un paciente del Grupo Ropi y tres pacientes del Grupo Bupi, quedaron excluidos del estudio por fallos de bloqueo. La reducción de la CVF en el Grupo Ropi se hizo máxima a los 30 minutos (25,1 por ciento) y a partir de entonces, hubo una tendencia progresiva a la recuperación. Ya con la bupivacaína, la reducción de la CVF pareció ser menos acentuada en los diversos momentos estudiados; se observó una reducción adicional entre 30 minutos (15,8 por ciento) y 4 horas (17,3 por ciento), siendo esa sin diferencia estadística. A partir de 4 horas, se notó una tendencia a la recuperación. En los dos grupos, después de 6 horas de bloqueo, la CVF todavía estaba por debajo de los valores previos. CONCLUSIONES: El bloqueo interescalénico reduce la CVF en la mayoría de los casos; las alteraciones fueron más acentuadas en el Grupo Ropivacaína.
Subject(s)
Adult , Female , Humans , Male , Amides/pharmacology , Anesthetics, Local/pharmacology , Brachial Plexus , Bupivacaine/pharmacology , Nerve Block , Vital Capacity/drug effects , Amides/administration & dosage , Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Double-Blind Method , Nerve Block/methodsABSTRACT
OBJETIVO: Avaliar a função pulmonar pós-colecistectomias subcostais abertas de pacientes sob ação da morfina no pós-operatório imediato. MÉTODOS: Tratou-se de um estudo prospectivo, onde se avaliaram espirometrias pós-operatórias de 15 pacientes submetidas à colecistectomias abertas subcostais, que receberam dose única de morfina peridural na anestesia. Os dados pós-operatórios foram comparados aos pré-operatórios pelo teste t-Student emparelhado. Um valor de p < 0,05 foi considerado estatisticamente significativo. RESULTADOS: Existiram diferenças significativas para as variáveis Capacidade Vital Forçada (p = 0,007) e Volume Expiratório Forçado no 1º segundo (p = 0,008) no pré e pós-operatório imediato, indicando distúrbios ventilatórios restritivos. Todas as pacientes apresentaram espirometrias normais no 3º dia de pós-operatório. CONCLUSÃO: Mesmo sob ação analgesia da morfina peridural, no pós-operatória imediato, foram observados distúrbios ventilatórios restritivos leves pós-colecistectomias subcostais abertas. Contudo, observou-se uma rápida recuperação da função pulmonar, o que pode diminuir a morbidade pulmonar pós-operatória.
OBJECTIVE: To evaluate pulmonary function after open subcostal cholecystecomy under action of the morphine in the immediate post-operative. METHODS: This was a prospective study, in which the post-operative spirometries of fifteen patients who underwent open subcostal cholecystectomies which received peridural morphine anesthesia. Post- and pre-operative data were compared using a paired student-t test. A value of p < 0,05 was considered statistically significant. RESULTS: Significant differences existed for the Forced Vital Capacity variable (p = 0,007) and Forced Expiratory Volume in the first second (p = 0,008) between pre- and immediate post-operative, indicating restrictive ventilatory disturbances. All of the patients presented normal espirometries in the third day of post-operative. CONCLUSION: Even under action morphine peridural analgesia, in the immediate post-operative, light restrictive post-cholecystectomy ventilatory disturbances were observed. However, it was observed abbreviated recovery of pulmonary function, which may lower post-operative pulmonary morbidity.
Subject(s)
Adult , Humans , Analgesics, Opioid/pharmacology , Cholecystectomy/methods , Forced Expiratory Volume/drug effects , Morphine/pharmacology , Vital Capacity/drug effects , Prospective StudiesABSTRACT
OBJECTIVES: To evaluate the effects of intrathecal morphine on pulmonary function, analgesia, and morphine plasma concentrations after cardiac surgery. INTRODUCTION: Lung dysfunction increases morbidity and mortality after cardiac surgery. Regional analgesia may improve pulmonary outcomes by reducing pain, but the occurrence of this benefit remains controversial. METHODS: Forty-two patients were randomized for general anesthesia (control group n=22) or 400 µg of intrathecal morphine followed by general anesthesia (morphine group n=20). Postoperative analgesia was accomplished with an intravenous, patient-controlled morphine pump. Blood gas measurements, forced vital capacity (FVC), forced expiratory volume (FEV), and FVC/FEV ratio were obtained preoperatively, as well as on the first and second postoperative days. Pain at rest, profound inspiration, amount of coughing, morphine solicitation, consumption, and plasma morphine concentration were evaluated for 36 hours postoperatively. Statistical analyses were performed using the repeated measures ANOVA or Mann-Whiney tests (*p<0.05). RESULTS: Both groups experienced reduced FVC postoperatively (3.24 L to 1.38 L in control group; 2.72 L to 1.18 L in morphine group), with no significant decreases observed between groups. The two groups also exhibited similar results for FEV1 (p=0.085), FEV1/FVC (p=0.68) and PaO2/FiO2 ratio (p=0.08). The morphine group reported less pain intensity (evaluated using a visual numeric scale), especially when coughing (18 hours postoperatively: control group= 4.73 and morphine group= 1.80, p=0.001). Cumulative morphine consumption was reduced after 18 hours in the morphine group (control group= 20.14 and morphine group= 14.20 mg, p=0.037). The plasma morphine concentration was also reduced in the morphine group 24 hours after surgery (control group= 15.87 ng.mL-1 and morphine group= 4.08 ng.mL-1, p=0.029). CONCLUSIONS: Intrathecal morphine administration did not ...
Subject(s)
Female , Humans , Male , Middle Aged , Analgesics, Opioid/pharmacology , Lung/drug effects , Morphine/pharmacology , Analysis of Variance , Anesthesia, General , Analgesics, Opioid/blood , Blood Gas Analysis , Coronary Artery Bypass , Forced Expiratory Volume/drug effects , Injections, Spinal , Morphine/blood , Pain Measurement/drug effects , Pain, Postoperative/drug therapy , Spirometry , Statistics, Nonparametric , Vital Capacity/drug effectsABSTRACT
OBJETIVO: Correlacionar a capacidade inspiratória (CI), por cento do previsto, pós-broncodilatador (pós-BD), com outras variáveis indicativas de gravidade e prognóstico, na doença pulmonar obstrutiva crônica (DPOC). MÉTODOS: Oitenta pacientes estáveis com DPOC realizaram manobras de capacidade vital forçada, capacidade vital lenta, e teste de caminhada de 6 min, antes e após salbutamol spray (400 µg). Foram divididos em quatro grupos, segundo o volume expiratório forçado no primeiro segundo pós-BD. Diversas variáveis foram testadas, por análise univariada e multivariada, com a distância caminhada pós-BD, por cento do previsto. A CI pós-BD foi correlacionada com o estadiamento Global Initiative for Chronic Obstructive Lung Disease (GOLD) e o índice Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE). RESULTADOS: Por análise de regressão multivariada, a CI pós BD, por cento do previsto, (p = 0,001), o uso de oxigênio a longo prazo (p = 0,014), e o número de medicamentos usados (p = 0,044), mantiveram associação significativa com a distância caminhada, por cento do previsto. A CI < 70 por cento foi observada em 56 por cento dos pacientes em estágios GOLD 3 ou 4 comparado a 20 por cento em estágios GOLD 1 ou 2 ( p < 0,001). A CI < 70 por cento foi observada em 60 por cento dos pacientes com escore BODE 3 ou 4 vs. 33 por cento com BODE 1 ou 2 (p = 0,02). CONCLUSÃO: A CI, por cento do previsto, pós-BD é o melhor preditor funcional da distância caminhada, associando-se significativamente com o escore GOLD e o índice BODE. Por isso, propomos que a CI seja incluída na rotina de avaliação dos portadores de DPOC.
OBJECTIVE: To correlate the postbronchodilator (post-BD) inspiratory capacity (IC), percent of predicted, with other markers of severity and prognostic factors in chronic obstructive pulmonary disease (COPD). METHODS: Eighty stable patients with COPD performed forced vital capacity and slow vital capacity maneuvers, as well as the 6-min walk test, prior to and after receiving albuterol spray (400 µg). Patients were divided into four groups, based on post-BD forced expiratory volume in one second. Several variables were tested to establish correlations with the post-BD distance walked, using univariate and multivariate analysis. Post-BD IC was found to correlated with Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging and with the Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) index. RESULTS: Multivariate regression analysis revealed that the distance walked, percent predicted, correlated significantly with the IC post-BD, percent predicted (p = 0.001), long-term oxygen use (p = 0.014), and number of medications used in the treatment (p = 0.044). IC < 70 percent was observed in 56 percent patients in GOLD stages 3 or 4 vs. 20 percent in GOLD 1 or 2 (p < 0.001). IC < 70 percent was observed in (60 percent) patients with BODE score 3 or 4 vs. (33 percent) BODE score 1 or 2 (p = 0.02). CONCLUSION: Post-BD IC percent predicted is the best functional predictor of distance walked and is significantly associated with GOLD staging and BODE index. Therefore, We propose that the inspiratory capacity should be added to the routine evaluation of the COPD patients.
Subject(s)
Aged , Female , Humans , Male , Albuterol/administration & dosage , Bronchodilator Agents/administration & dosage , Exercise Tolerance , Inspiratory Capacity , Pulmonary Disease, Chronic Obstructive/diagnosis , Airway Obstruction/physiopathology , Body Mass Index , Cross-Sectional Studies , Dyspnea/physiopathology , Exercise Test/drug effects , Exercise Test/methods , Exercise Tolerance/drug effects , Exercise Tolerance/physiology , Forced Expiratory Volume/drug effects , Forced Expiratory Volume/physiology , Inspiratory Capacity/drug effects , Inspiratory Capacity/physiology , Prognosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Regression Analysis , Severity of Illness Index , Statistics, Nonparametric , Time Factors , Vital Capacity/drug effects , Vital Capacity/physiology , Walking/physiologyABSTRACT
OBJETIVO: Analisar, através da técnica de oscilações forçadas, pacientes asmáticos com resposta broncodilatadora positiva pelo laudo espirométrico e comparar esses resultados com os obtidos em indivíduos sadios. MÉTODOS: Foram analisados 53 indivíduos não tabagistas, sendo 24 sadios sem história de doença pulmonar e 29 asmáticos com resposta broncodilatadora positiva segundo o laudo espirométrico. Todos foram submetidos à técnica de oscilações forçadas e a espirometria antes e após vinte minutos da administração de salbutamol spray (300 g). Os parâmetros derivados da técnica de oscilações forçadas foram: resistência total, reatância total, resistência extrapolada para o eixo y, coeficiente angular da reta de resistência e complacência dinâmica. Na espirometria, os parâmetros utilizados foram o volume expiratório forçado no primeiro segundo e a capacidade vital forçada. RESULTADOS: No grupo controle, a utilização do broncodilatador produziu alteração significativa na resistência extrapolada para o eixo y (p < 0,001), embora o coeficiente angular da reta de resistência e a complacência dinâmica não tenham apresentado diferenças estatisticamente significativas. A análise dos asmáticos mostrou que a diferença entre as medidas pré e pós-broncodilatador foi significativa, tanto para os parâmetros espirométricos quanto para os de técnica de oscilações forçadas. Valores de p < 0,001 foram obtidos em todas as comparações relacionadas aos asmáticos. CONCLUSÃO: As alterações nos parâmetros obtidos a partir da técnica de oscilações forçadas mostraram-se em estreita concordância com a fisiopatologia da resposta broncodilatadora em asmáticos, indicando que a técnica de oscilações forçadas pode ser útil como análise complementar à espirometria nesses pacientes.