Course Of FEV1 Research Articles

Risk factors for the deterioration of pulmonary function in primary ciliary dyskinesia.

PCD is a genetic disease leading to a decline in pulmonary function. There is only little knowledge of factors determining the long-term pulmonary outcome. Especially adherence has not been addressed yet although being an independent risk factor for an increased loss of lung capacity in other chronic respiratory diseases. Assessing the impact of bacterial airway colonization and adherence on long-term lung function in patients with PCD. Data on colonization and lung function parameters like forced expiratory volume in the first second (FEV1, Z-score) and lung clearance index (LCI2,5% ) were collected for 7.01 ± 2.2 years (893 quarters) in 44 PCD patients. Adherence was classified as good, moderate or poor. The impact of both adherence and colonization was assessed for the long-term course of FEV1, the association of colonization with lung function also quarterly. Kruskall-Wallis test, T test, ANOVA, linear regression, linear mixed model. Chronic colonization did not show any impact on the for long-term course of FEV1 , but adherence was a significant factor: patients with good adherence showed better FEV1 at the end of the observation period than children with poor adherence (-0.15 ± 0.88 vs. -2.63 ± 1.79, p < 0.01). Adherence has not yet been investigated for PCD. However, we found it to be a major significant factor affecting long-term FEV1 in PCD. Thus, it should be taken into consideration in the treatment protocols for PCD.

Impact of Lung Function Decline on Mortality in Lung Transplant Recipients: Long-Term Results From the L-CsA-i Study for the Prevention of Bronchiolitis Obliterans Syndrome.

BackgroundChronic lung allograft dysfunction (CLAD) is defined by a progressive loss of FEV1 and is associated with premature mortality. The aim of this study was to investigate the direct association between FEV1 decline and risk of mortality in patients after lung transplantation (LTx).Methods10-year follow up data from lung transplant recipients participating in randomized placebo-controlled clinical trial investigating the role of liposomal Cyclosporine A for inhalation (L-CsA-i) in the prevention of bronchiolitis obliterans syndrome (NCT01334892) was used. The association between the course of FEV1 over time and the risk of mortality was assessed using joint modeling and Cox regression analysis.ResultsA total of 130 patients were included. Predictors of FEV1 decline were a higher absolute FEV1 at baseline and male sex. The joint model analysis indicated a significant association of change of FEV1 and risk of mortality (p < 0.001), with a predicted 3.4% increase in mortality risk for each 1% decline in FEV1. Significant predictors of a progressive phenotype were single LTx and treatment with placebo (as opposed to L-CsA-i). At the end of follow-up, 82 patients (63.1%) were still alive. Cox regression analyses for mortality identified only single LTx as a predictor of higher risk.ConclusionBased on our observation of a close association between FEV1 and mortality over a period of 10 years we suggest FEV1 as a valid predictor of mortality and a suitable surrogate endpoint in the investigation of early interventions.

Data-driven adult asthma phenotypes based on clinical characteristics are associated with asthma outcomes twenty years later.

Research based on cluster analyses led to the identification of particular phenotypes confirming phenotypic heterogeneity of asthma. The long-term clinical course of asthma phenotypes defined by clustering analysis remains unknown, although it is a key aspect to underpin their clinical relevance. We aimed to estimate risk of poor asthma events between asthma clusters identified 20years earlier. The study relied on two cohorts of adults with asthma with 20-year follow-up, ECRHS (European Community Respiratory Health Survey) and EGEA (Epidemiological study on Genetics and Environment of Asthma). Regression models were used to compare asthma characteristics (current asthma, asthma exacerbations, asthma control, quality of life, and FEV1 ) at follow-up and the course of FEV1 between sevencluster-based asthma phenotypes identified20years earlier. The analysis included 1325 adults with ever asthma. For each asthma characteristic assessed at follow-up, the risk for adverse outcomes differed significantly between the seven asthma clusters identified at baseline. As compared with the mildest asthma phenotype, ORs (95% CI) for asthma exacerbations varied from 0.9 (0.4 to 2.0) to 4.0 (2.0 to 7.8) and the regression estimates (95% CI) for FEV1 % predicted varied from 0.6 (-3.5 to 4.6) to -9.9 (-14.2 to -5.5) between clusters. Change in FEV1 over time did not differ significantly across clusters. Our findings show that the long-term risk for poor asthma outcomes differed between comprehensive adult asthma phenotypes identified 20years earlier, and suggest a strong tracking of asthma activity and impaired lung function over time.

Prognostic significance of early pulmonary function changes after onset of chronic lung allograft dysfunction.

Chronic lung allograft dysfunction (CLAD), including the phenotypes of bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (R-CLAD), represents the leading cause of late death after lung transplantation. Little is known, however, regarding the natural history or prognostic significance of pulmonary function changes after the onset of these conditions. We examined changes in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) over the first 18 months after CLAD. We also sought to determine whether lung function changes occurring early after CLAD impact longer term outcomes. We performed a retrospective analysis of 216 bilateral lung recipients with CLAD, which included those with R-CLAD (n = 65) or BOS (n = 151). The course of FEV1 and FVC after CLAD was described. Cox proportional hazards models were used to evaluate the impact of a ≥10% decline in FEV1 or FVC within the first 6 months of CLAD on graft loss after that time. Lung recipients with CLAD, whether BOS or R-CLAD, had the largest decreases in FEV1 and FVC within the first 6 months after onset. Moreover, a decline in FEV1 or FVC of ≥10% within the first 6 months after CLAD was associated with a significantly increased hazard for graft loss after that time (hazard ratio [HR] = 3.17, 95% confidence interval [CI] 1.56 to 6.42, p = 0.001, and HR = 2.80, 95% CI 1.66 to 4.70, p ≤ 0.001, respectively), an effect observed in both BOS and R-CLAD patients. Early physiologic changes after CLAD were independently associated with graft loss. This suggests lung function changes after CLAD, specifically a ≥10% decline in FEV1 or FVC, could be a surrogate measure of graft survival.

Regulatory T Cells Correlate with Percent Predicted FEV1 after Lung Transplantation

Purpose: Regulatory T cells (Treg) possibly contribute significantly to allograft survival and may counteract the development of BOS in lung transplant patients. Clinically, the most valuable parameter of lung allograft function is the %predicted FEV1 measured in spirometry. It is used for diagnosis of both acute and chronic rejection episodes and high values may thus represent an immunologically favourable course. In this analysis, we present a cohort of 89 patients, in which we analyzed Tregs after lung transplantation as well as lung function results. Methods and Materials: In all patients, the number of circulating Tregs was measured by flow cytometry 3 weeks as well as 3 months, 6 months and 12 months after transplantation. Putative Treg were defined as CD4+CD25high T cells and were further analyzed for different surface as well as intracellular molecules such as CD152, CD127 as well as FoxP3. Additionally, lung function results at the time points 3 weeks, 3 months, 6 months and 12 months after transplantation were analyzed. After performing a Spearmans test of correlation, the cohort was divided into two groups based on the postoperative course of FEV1. A loss of 10% of FEV1 defining an unfavourable course implying the development of BOS whereas a stable FEV1 was defined as stable postoperative development. With these two groups, a repeated measure ANOVA test was performed monitoring the different surface molecules. Results: A total of 89 patients were included into the study. The Spearmans test of correlation revealed a statistically significant correlation between the %predicted FEV1 measured 3 weeks after transplantation and the number of CD127low Treg (p< 0.05). Similar results were detectable between %predicted FEV1 at 3 months postoperatively and CD152+ (CTLA-4) Treg (p< 0.05) as well as CD4+CD25+ Treg and %predicted FEV1 6 months postoperatively (p< 0.05). Repeated measure ANOVA test revealed a statistically significant result relating the clinical course in the first postoperative year - defined by the course of %predicted FEV1- to the number of FoxP3+ Treg circulating in the peripheral blood (p< 0.05). Conclusions: The number of circulating Treg in the peripheral blood may indicate a favourable immunologic course after lung transplantation resulting in better %predicted FEV1 in the first year after transplantation.

Level and course of FEV1 in relation to polymorphisms in NFE2L2 and KEAP1 in the general population

BackgroundThe metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second (FEV1) in the general population.MethodsFive NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 FEV1 measurements during 3 surveys, respectively 7 FEV1 measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated FEV1 measurements.ResultsIn the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher FEV1 level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower FEV1 level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of KEAP1 or NFE2L2 SNPs with FEV1 decline was observed.ConclusionThis is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population. It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of FEV1 in the general population. It additionally shows that NFE2L2 and KEAP1 variations are unlikely to play a role in the longitudinal course of FEV1 in the general population.

Long-Term Azithromycin for Bronchiolitis Obliterans Syndrome After Lung Transplantation

Bronchiolitis obliterans syndrome (BOS) is a major cause of morbidity and mortality after lung transplantation (LTx). Macrolides are a promising treatment option for BOS. The objective of this study was to determine long-term results of azithromycin treatment in patients with BOS. Variables to predict treatment response were evaluated. An observational study in a single center was performed. Eighty-one adult LTx-recipients (single, double, combined, and re-do) with at least BOS stage 0p (mean forced expired volume in 1 second [FEV1] 55+/-19%) were included. For treatment, 250 mg of oral azithromycin was administered three times per week. Twenty-four of 81 (30%) patients showed improvement in FEV1 after 6 months, 22/24 already after 3 months of treatment. By univariate analysis, responders at 6 months had higher pretreatment bronchoalveolar lavage (BAL) neutrophils (51+/-29 vs. 21+/-24%). A cutoff value of <20% in pretreatment BAL had a negative predictive value of 0.91 for treatment response. Thirty-three patients (40%) showed disease progression during follow-up (491+/-165 days). Cox regression analysis identified a rapid pretreatment decline in FEV1 and comedication of an mammalian target of rapamycin inhibitor as positive predictors and proton pump inhibitor comedication and a treatment response at 3 months as negative predictors for disease progression (FEV1<90% baseline). Azithromycin can improve airflow limitation in a significant proportion of patients with even long-standing BOS. The majority of responders were identified after 3 months of treatment. Results indicate the predictive value of BAL neutrophilia for treatment response and pretreatment course of FEV1 as a variable for disease progression. Beneficial effects on gastroesophageal reflux disease may be a mechanism of action.

Successful lung volume reduction surgery brings patients into better condition for later lung transplantation.

Lung volume reduction surgery (LVRS) is accepted as a potential alternative therapy to lung transplantation (LTX) for selected patients. However, the possible impact of LVRS on a subsequent LTX has not been clearly elucidated so far. We therefore analyzed the course of 27 patients who underwent LVRS followed by LTX in our institution. Twenty-seven patients (11 male, 16 female, mean age 51.9+/-2.2 years) out of 119 patients who underwent LVRS between 1994 and 1999 underwent LTX 29.7+/-3.2 months (range 2-57 months) after LVRS. Based on the postoperative course of FeV1 after LVRS (best value within the first 6 months postoperatively compared with the preoperative value) patients were divided into two groups: Group A (n=11) without any improvement (FeV1 <20% increase), and Group B (n=16) with FeV1 increase > or = 20% after successful LVRS which declined to preoperative values after 8-42 months. Subsequent LTX was performed 22.9+/-5.6 months after LVRS in Group A and 34.3+/-4.9 months after LVRS in Group B (P<0.05). Patients were analyzed according to the course of their functional improvement and of their body mass index (BMI) after LVRS and to survival after LTX, respectively. Values are given as the mean+/-SEM and significance was calculated by the chi(2)-test whereas continuous values were estimated by Student's t-test. Patients in Group A without improvement in FeV1 after LVRS had no increase in BMI as well and this resulted in a high perioperative mortality of 27.3% after LTX. On the contrary, patients in Group B, who had a clear increase of FeV1 after LVRS, experienced a significant increase of BMI of 23.2+/-4.5% as well (P<0.05). This improvement in BMI remained stable despite a later deterioration of FeV1 prior to LTX. After LTX, these patients had a significantly lower perioperative mortality of 6.3% as compared to Group A (P=0.03). Successful LVRS delays the need for transplantation, improves nutritional status and brings patients into a better pretransplant condition, which results in decreased perioperative mortality at LTX. Patients after failed LVRS, however, should be considered as poor candidates for later transplantation.

Long term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis

BACKGROUNDThe role of inhaled corticosteroids in the long term management of chronic obstructive pulmonary disease (COPD) is still unclear. A meta-analysis of the original data sets of the randomised controlled...

Moderately severe chronic airflow obstruction. Can corticosteroids slow down obstruction?

In a former study in patients with severe chronic airflow obstruction (CAO), (forced expiratory volume in one second (FEV1) ranging from 350-910 ml), we concluded that daily oral corticosteroids might slow down the progression of disease. The results of the present long-term (14-20 yr) study on 139 non-allergic patients with less severe CAO (FEV1 greater than or equal to 1200 ml, FEV1 as a percentage of vital capacity (FEV1%VC) 40-55%) confirm and extend our former observations. Four patterns of the course of FEV1 and inspiratory vital capacity (VC) in time were recognized: 1) linear decrease; 2) no change; 3) initial increase, followed by decrease; 4) initial decrease, followed by increase. Groups 1 and 3 had a higher functional residual capacity as a percentage of total lung capacity (FRC%TLC) as compared to group 2 and 4; the work of breathing was lower in group 2 than in the other three groups. Otherwise the initial 82 parameters, including the degree of reversibility of airflow obstruction and smoking habits were comparable in the four groups. The four patterns of FEV1 showed a strong association with the long-term use of prednisolone. When oral prednisolone was instituted or increased to a dose of at least 10 mg/day continuously, FEV1 either remained constant, decreased more slowly or even increased over many years of follow-up. When the oral dose was diminished to below 10 mg/day, FEV1 decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Independent influence of reversibility of air-flow obstruction and nonspecific hyperreactivity on the long-term course of lung function in chronic air-flow obstruction.

We evaluated factors that might influence the course of lung function after 2 to 21 yr of follow-up in 81 nonallergic patients with chronic air-flow obstruction (CAO) and considerable lung function impairment (initial forced expiratory volume in one second as a percentage of inspiratory slow vital capacity (FEV1 % VC) ranging from 40 to 55% and increasing less than 15% after the administration of the anticholinergic bronchodilator thiazinamium). A more favorable rate of change in FEV1 was associated with less pack-years of smoking, less nonspecific hyperreactivity, and a higher degree of reversibility of air-flow obstruction, when expressed as the increase in FEV1 as a percentage of the predicted minus prebronchodilator FEV1 value. Nonspecific hyperreactivity and reversibility of air-flow obstruction appeared to influence the decline in FEV1 independently of baseline value of FEV1, both in smokers and ex-smokers. The hypothesis is put forward that regular bronchodilating therapy may be able to prevent deterioration of lung function. However, the possibility that interval therapy may ultimately produce the same results cannot be excluded. It seems to be important to stop smoking, both for the sake of its negative influence on the course of FEV1 and for the fact that a beneficial influence of bronchodilating therapy may become even more apparent.

PROPRANOLOL INHALATION IN CHILDREN WITH ASTHMA

Inhalation of propranolol (P), a non-selective beta blocker, induces a bronchial constriction in many patients with asthma. In adults P challenge has been used for estimation of hyperreactivity. Untill now no reports are available on P challenge in children. In 65 children with asthma aged 8-14 yr we consecutively performed a histamine provociation test and after recovery from bronchoconstriction a P challenge. In 45 children P challenges were performed in the same way as in adults, with dosages increasing in steps of 0,25 mg from 0,25 to 1,5 mg. In 20 children a modified method was used, doubling the concentration of P at each inhalation (0,1-1,6 mg%). In another 20 children the course of FEV1 after P challenge was studied. The aim of the study was to investigate the feasibility of P challenges in children and to establish the relation with histamine provocation tests. The findings are: - P threshold was found in 60% of the children with a response to histamine. This is in agreement with findings in adults. - The correlation between histamine and P thresholds is slight (r=.34). - Most children have an increase of bronchoconstriction 15 min. after challenge with P. - Severe bronchoconstriction induced by P can be blocked by inhalation of ipatropiumbromide. - Recovery after P challenge is slow and lasts for more than 2 hrs. - P challenge is less suitable for clinical estimation of hyperreactivity. It can be applied for research on basic mechanisms of patterns of bronchial constriction in patients with astma.