Daily or intermittent budesonide in preschool children with recurrent wheezing.

N Engl J Med. 2011 Nov 24;365(21):1990-2001

Authors: Zeiger RS, Mauger D, Bacharier LB, Guilbert TW, Martinez FD, Lemanske RF, Strunk RC, Covar R, Szefler SJ, Boehmer S, Jackson DJ, Sorkness CA, Gern JE, Kelly HW, Friedman NJ, Mellon MH, Schatz M, Morgan WJ, Chinchilli VM, Raissy HH, Bade E, Malka-Rais J, Beigelman A, Taussig LM,

Abstract
BACKGROUND: Daily inhaled glucocorticoids are recommended for young children at risk for asthma exacerbations, as indicated by a positive value on the modified asthma predictive index (API) and an exacerbation in the preceding year, but concern remains about daily adherence and effects on growth. We compared daily therapy with intermittent therapy.
METHODS: We studied 278 children between the ages of 12 and 53 months who had positive values on the modified API, recurrent wheezing episodes, and at least one exacerbation in the previous year but a low degree of impairment. Children were randomly assigned to receive a budesonide inhalation suspension for 1 year as either an intermittent high-dose regimen (1 mg twice daily for 7 days, starting early during a predefined respiratory tract illness) or a daily low-dose regimen (0.5 mg nightly) with corresponding placebos. The primary outcome was the frequency of exacerbations requiring oral glucocorticoid therapy.
RESULTS: The daily regimen of budesonide did not differ significantly from the intermittent regimen with respect to the frequency of exacerbations, with a rate per patient-year for the daily regimen of 0.97 (95% confidence interval [CI], 0.76 to 1.22) versus a rate of 0.95 (95% CI, 0.75 to 1.20) for the intermittent regimen (relative rate in the intermittent-regimen group, 0.99; 95% CI, 0.71 to 1.35; P=0.60). There were also no significant between-group differences in several other measures of asthma severity, including the time to the first exacerbation, or adverse events. The mean exposure to budesonide was 104 mg less with the intermittent regimen than with the daily regimen.
CONCLUSIONS: A daily low-dose regimen of budesonide was not superior to an intermittent high-dose regimen in reducing asthma exacerbations. Daily administration led to greater exposure to the drug at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; MIST ClinicalTrials.gov number, NCT00675584.).

PMID: 22111718 [PubMed - indexed for MEDLINE]

Prognostic factors for idiopathic pulmonary fibrosis: clinical, physiologic, pathologic, and molecular aspects.

Sarcoidosis Vasc Diffuse Lung Dis. 2011 Oct;28(2):102-12

Authors: Lee SH, Shim HS, Cho SH, Kim SY, Lee SK, Son JY, Jung JY, Kim EY, Lim JE, Lee KJ, Park BH, Kang YA, Kim YS, Kim SK, Chang J, Park MS

Abstract
BACKGROUND: Previous studies identified clinical and physiologic factors of idiopathic pulmonary fibrosis (IPF) that are related to an increased risk of mortality. But there are few studies about histologic and molecular approach.
OBJECTIVE: We investigated whether the C-reactive protein (CRP), fibroblastic foci, phosphorylated Smad2/3 (p-Smad2/3), tumor growth factor-beta (TGF-beta), TGF-beta receptor II (TbetaRII), and the polymorphism of the TGF-beta1 codon 10 are associated with the progression of IPF patients.
DESIGN: Eighty-six IPF patients who underwent surgical lung biopsies were examined. For each patient, clinical and physiologic parameters were investigated, and we performed immunohistochemical staining for p-Smad2/3 and TbetaRII, and genotyping of the TGF-beta1 codon 10 polymorphism.
RESULTS: Age at diagnosis, gender, symptom duration, and smoking status did not show a significant association. However, the amount of smoking (p = 0.002), severe reduction in the percentages of predicted forced vital capacity (p = 0.013) and diffusion lung capacity of carbon monoxide (p = 0.023), CRP (p = 0.009) at diagnosis, and fibroblastic foci (p = 0.026) were associated with a poor prognosis. Cellularity, fibrosis, expression level of p-Smad2/3 and TbetaRII, and genotype of the TGF-beta1 codon 10 polymorphism did not have a statistically significant association with the prognosis.
CONCLUSION: This study confirmed the amount of smoking, abrupt decrease in follow-up pulmonary function parameters, fibroblastic foci, and increased levels of CRP concentration at diagnosis were significantly associated with poor survival. Larger studies are required to confirm all prognostic factors including CRP.

PMID: 22117501 [PubMed - indexed for MEDLINE]

18F-FDG PET as a predictor of pulmonary function in sarcoidosis.

Sarcoidosis Vasc Diffuse Lung Dis. 2011 Oct;28(2):123-9

Authors: Keijsers RG, Verzijlbergen EJ, van den Bosch JM, Zanen P, van de Garde EM, Oyen WJ, Grutters JC

Abstract
PURPOSE: Fluor-18 fluorodeoxyglucose (18F-FDG) PET is able to demonstrate sarcoidosis activity. Ongoing pulmonary sarcoidosis activity can be reflected by a decline in pulmonary function tests (PFT). To assess whether diffuse metabolic activity of the lung parenchyma imaged by 18F-FDG PET predicts future pulmonary deterioration, 18F-FDG PET was compared with PFT.
METHODS: In this retrospective cohort study, 43 newly diagnosed, sarcoidosis patients were analyzed. Based on 18F-FDG PET, patients were diagnosed with diffuse parenchymal disease activity, without or with immunosuppressive treatment, started after 18F-FDG PET was performed. As a control, sarcoidosis patients with mediastinal/hilar disease activity but without metabolic activity in the lung parenchyma were analyzed, all without treatment. Vital capacity (VC), forced expiratory volume (FEV1) and diffusion capacity of the lung for carbon monoxide (DLCO) were analyzed per group at baseline, i.e., at the time 18F-FDG PET was performed, and after one year follow-up.
RESULTS: At follow-up, a significant decrease in DLCO was found in untreated patients with diffuse parenchymal activity. No change in VC or FEV1 could be observed. Treated patients with parenchymal activity showed a significant increase in VC, FEV1 and DLCO, while patients without parenchymal activity did not show any change in PFT.
CONCLUSIONS: In sarcoidosis, diffuse parenchymal disease imaged by 18F-FDG PET, predicts a future deterioration of DLCO when untreated. Treatment however, improves VC, FEV1 and DLCO significantly suggesting that 18F-FDG PET represents the pulmonary improvement that can be achieved. The absence of metabolic activity in the lung parenchyma justifies a wait-and-see policy.

PMID: 22117503 [PubMed - indexed for MEDLINE]

BACKGROUND: The optimal means of quantifying change on chest radiography in sarcoidosis is uncertain. In current guidelines, the role of serial measurement of carbon-monoxide diffusing capacity (DLco) remains undefined and the prevalence of discordance between serial chest radiographic change and pulmonary function tends is unknown.

OBJECTIVE: To identify and explore key uncertainties in the monitoring of sarcoidosis by serial pulmonary function tests and chest radiography.
DESIGN: 354 patients with sarcoidosis and concurrent tests (chest radiography and PFTs within three months at baseline, two years and/or four years) were studied. Chest radiographs were assessed by two radiologists for changes in stage and disease extent. Radiographic change and pulmonary function trends were quantified and compared.
RESULTS: Change in radiographic extent of lung disease was always more frequent than change in stage (p < 0.0001) and there was poor agreement between change in stage and change in radiographic extent (Kw = 0.21 at two years; Kw = 0.23 at four years). Change in disease extent on chest radiography was linked to PFT trends on analysis of variance (p < 0.0005 for FEV1, FVC, DLco), whereas change in radiographic stage was not. Changes in gas transfer were often isolated or discordant with other serial data. Discordance between pulmonary function data and chest radiographic data was observed in 50% of cases.
CONCLUSIONS: Change in radiographic extent is more applicable to routine monitoring in sarcoidosis than change in radiographic stage. In future guidelines, the role of serial gas transfer estimation and reconciliation of divergent chest radiographic and functional trends might usefully be addressed.