Change In FVC Research Articles

Salmeterol/fluticasone through breath-actuated inhaler versus pMDI: a randomized, double-blind, 12 weeks study

Objective: Salmeterol/fluticasone combination (SFC) formulated in a breath-actuated inhaler (BAI) overcomes the co-ordination problem associated with the pressurized-metered dose inhaler (pMDIs). Our aim was to compare the efficacy and the safety of SFC given through the BAI versus the conventional pMDI in moderate-to-severe asthmatics. Methods: In this randomized, double-blind, double-dummy, prospective, active-controlled, parallel group, multicenter, 12 weeks study, 150 asthmatics were randomized to receive SFC (25/125 mcg) through either BAI or pMDI. The primary efficacy endpoint was mean change in pre-dose morning PEFR value at 12 weeks and the secondary efficacy endpoints included, mean change in FEV1, pre-bronchodilator FVC, pre-dose morning and evening PEFR, symptom scores at 2, 4, 8, and 12 weeks. Patient preferences for device and safety were also assessed. Results: At 12 weeks, the mean change in pre-dose morning PEFR in BAI and pMDI groups was 50.72 L/min and 48.82 L/min, respectively (p < 0.0001; both groups) and the difference between the two groups was not significant. Both the treatment groups showed a statistically significant improvement in secondary endpoints at all-time points compared with baseline. The usability questionnaire assessment results showed that the BAI device was preferred by 75% of patients as compared with 25% preferring pMDI. SFC in both BAI and pMDI devices was found to be safe and well tolerated. Conclusion: This is the first study to demonstrate that SFC given through the BAI produces comparable efficacy and safety endpoints as pMDI. Additionally, BAI was the preferred inhaler by patients compared to conventional pMDI.

Sensitivity Analyses of the Change in FVC in a Phase 3 Trial of Pirfenidone for Idiopathic Pulmonary Fibrosis

FVC outcomes in clinical trials on idiopathic pulmonary fibrosis (IPF) can be substantially influenced by the analytic methodology and the handling of missing data. We conducted a series of sensitivity analyses to assess the robustness of the statistical finding and the stability of the estimate of the magnitude of treatment effect on the primary end point of FVC change in a phase 3 trial evaluating pirfenidone in adults with IPF. Source data included all 555 study participants randomized to treatment with pirfenidone or placebo in the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND) study. Sensitivity analyses were conducted to assess whether alternative statistical tests and methods for handling missing data influenced the observed magnitude of treatment effect on the primary end point of change from baseline to week 52 in FVC. The distribution of FVC change at week 52 was systematically different between the two treatment groups and favored pirfenidone in each analysis. The method used to impute missing data due to death had a marked effect on the magnitude of change in FVC in both treatment groups; however, the magnitude of treatment benefit was generally consistent on a relative basis, with an approximate 50% reduction in FVC decline observed in the pirfenidone group in each analysis. Our results confirm the robustness of the statistical finding on the primary end point of change in FVC in the ASCEND trial and corroborate the estimated magnitude of the pirfenidone treatment effect in patients with IPF. ClinicalTrials.gov; No.: NCT01366209; URL: www.clinicaltrials.gov.

The effect of bronchodilators on forced vital capacity measurement in patients with idiopathic pulmonary fibrosis

BackgroundForced vital capacity (FVC) is a key measure of disease severity in patients with idiopathic pulmonary fibrosis (IPF) and is an important clinical trial endpoint. We hypothesize that reversible airflow limitation co-exists in a subgroup of patients with IPF, and that bronchodilator use will improve the performance characteristics of FVC. MethodsIPF patients with pre and post-bronchodilator spirometry testing performed were identified from two tertiary referral cohorts. The difference between pre and post-bronchodilator FVC (intra-test difference) was calculated. The test characteristics of pre and post-bronchodilator FVC change over time (inter-test difference) were assessed in patients with sequential spirometry, and were used to generate sample size estimates for hypothetical clinical trials using change in FVC as the primary endpoint. ResultsThere were 551 patients, contributing 967 unique spirometry tests. The mean intra-test increase in FVC with bronchodilator use was 0.04 L (2.71 vs. 2.75 L, p < 0.001). Reversible airflow limitation (increase in FEV1 or FVC of ≥12% and ≥200 mL) occurred in 9.1% of patients. The inter-test difference in change in FVC over time were equivalent for pre and post-bronchodilator (p = 0.65), leading to similar sample size estimates in a hypothetical clinical trial using change in FVC as the primary endpoint. ConclusionApproximately one in ten patients with IPF has physiological evidence of reversible airflow limitation, and bronchodilator use in these patients may improve the assessment of disease progression based on FVC change over time. Bronchodilator use does not appear to meaningfully impact the precision of FVC as an endpoint in clinical trials.

Impact of Varying Physical Activity Levels on Airway Responsiveness and Bronchodilation in Healthy Humans

Airway hyperresponsiveness is a hallmark symptom of asthma. In healthy subjects, there is variability in airway responsiveness (AR) to a given stimulus with inactive subjects exhibiting more AR compared to endurance-trained runners. Additionally, AR has been shown to be attenuated with endurance training and negatively associated with frequency of exercise; however, the quantity of physical activity needed to attenuate AR is not known. Also, it is not known if the bronchodilatory response to a stimulus can also be modified with exercise training. PURPOSE: Therefore, the purpose of this study was to determine if the amount of physical activity influenced AR and if a threshold exists at which higher physical activity levels would not further improve AR. A secondary purpose was to determine if the degree of bronchodilation would be affected across a range of PA levels. METHODS: 30 healthy subjects (21.9±2.6yrs; 13M/17W) with normal pulmonary function reported to the lab on two different occasions (randomized). On one visit, subjects performed a nebulized hypertonic saline (25%) (HS) challenge and the second visit consisted of the HS challenge followed by five deep maximal inspirations (DIs). In both conditions, pulmonary function tests (PFTs) were initially completed followed by breathing hypertonic saline mist for 20 minutes in the absence of deep breaths. Then, subjects either completed the PFTs or performed 5 DIs prior to performing PFTs. Moderate-to-vigorous physical activity (MVPA) level was measured via accelerometer worn for 7 days. RESULTS: Following the HS challenge, FEV1 and FVC significantly decreased ∼12% and ∼9%, respectively. Men and women had similar (p>0.05) changes in PFTs following the HS challenge. A two-segment linear model determined significant relationships between MVPA and percent change in FEV1 (r=0.52) and FVC (r=0.57). MVPA above ∼530 and ∼500 min/week for FEV1 and FVC, respectively resulted in minor additional improvements (p>0.05) in PFTs following the HS challenge. Following the DIs, FEV1 and FVC decreased (p<0.05) ∼7% and ∼5%, respectively, but were not related (p>0.05) to MVPA. CONCLUSION: These data provide evidence that higher MVPA levels ameliorated airway responsiveness, but not bronchodilation in healthy subjects. Additionally, it appears that MVPA above ∼500 minutes per week resulted in minor improvements in airway responsiveness in healthy subjects.

Longitudinal Forced Vital Capacity Monitoring as a Prognostic Adjunct after Lung Transplantation.

After lung transplantation, spirometric values are routinely followed to assess graft function. FEV1 is used to characterize chronic allograft dysfunction, whereas the course of FVC change has been less acknowledged and rarely used. To better understand the temporal relationship and prognostic ability of FEV1 and FVC decline after lung transplantation. Serial FEV1 and FVC values were studied among 205 bilateral lung transplant recipients. Different decline patterns were characterized and evaluated for prognostic value via restricted mean modeling of mortality and times to other pertinent events. Baseline FEV1 was achieved earlier than baseline FVC (median, 296 vs. 378 d; P < 0.0001). Decline in FEV1 or FVC from their respective post-transplant baselines occurred in 85 patients (41%). Fifty-nine of 85 (69%) had an isolated FEV1 decline, with 80% later meeting the FVC decline criterion. This subsequent FVC decline was associated with worsening FEV1 and lower median survival. Twenty-five of 85 patients (29%) demonstrated concurrent FEV1 and FVC decline. Patients with concurrent decline had higher 1- and 5-year mortality rates (1-yr, 53% vs. 18%, P < 0.0001; 5-yr, 61% vs. 48%, P = 0.001). These patients were more likely to have rapid-onset of spirometry decline (P = 0.05) and lower FEV1% predicted (P = 0.04) at presentation. FVC decline from its post-transplant baseline provides valuable prognostic information. Concurrent FEV1 and FVC decline identifies patients with fulminant, rapid deterioration and is the strongest clinical predictor of poor survival. Subsequent FVC decline in patients with an initial isolated FEV1 decline identifies disease progression and portends poor prognosis.

Adopting Clean Fuels and Technologies on School Buses. Pollution and Health Impacts in Children.

More than 25 million American children breathe polluted air on diesel school buses. Emission reduction policies exist, but the health impacts to individual children have not been evaluated. Using a natural experiment, we characterized the exposures and health of 275 school bus riders before, during, and after the adoption of clean technologies and fuels between 2005 and 2009. Air pollution was measured during 597 trips on 188 school buses. Repeated measures of exhaled nitric oxide (FeNO), lung function (FEV1, FVC), and absenteeism were also collected monthly (1,768 visits). Mixed-effects models longitudinally related the adoption of diesel oxidation catalysts (DOCs), closed crankcase ventilation systems (CCVs), ultralow-sulfur diesel (ULSD), or biodiesel with exposures and health. Fine and ultrafine particle concentrations were 10-50% lower on buses using ULSD, DOCs, and/or CCVs. ULSD adoption was also associated with reduced FeNO (-16% [95% confidence interval (CI), -21 to -10%]), greater changes in FVC and FEV1 (0.02 [95% CI, 0.003 to 0.05] and 0.01 [95% CI, -0.006 to 0.03] L/yr, respectively), and lower absenteeism (-8% [95% CI, -16.0 to -0.7%]), with stronger associations among patients with asthma. DOCs, and to a lesser extent CCVs, also were associated with improved FeNO, FVC growth, and absenteeism, but these findings were primarily restricted to patients with persistent asthma and were often sensitive to control for ULSD. No health benefits were noted for biodiesel. Extrapolating to the U.S. population, changed fuel/technologies likely reduced absenteeism by more than 14 million/yr. National and local diesel policies appear to have reduced children's exposures and improved health.

Lung function changes from childhood to adolescence: a seven-year follow-up study

BackgroundAs part of an investigation into the respiratory health in children conducted in Torino, northwestern Italy, our aim was to assess development in lung function from childhood to adolescence, and to assess changes or persistence of asthma symptoms on the change of lung function parameters. Furthermore, the observed lung function data were compared with the Global Lung Function Initiative (GLI) reference values.MethodsWe conducted a longitudinal study, which lasted 7 years, composed by first survey of 4–5 year-old children in 2003 and a follow-up in 2010. Both surveys consisted in collecting information on health by standardized SIDRIA questionnaire and spirometry testing with FVC, FEV1, FEV1/FVC% and FEF25–75 measurements.Results242 subjects successfully completed both surveys. In terms of asthma symptoms (AS = asthma attacks or wheezing in the previous 12 months), 191/242 were asymptomatic, 13 reported AS only in the first survey (early transient), 23 had AS only in the second survey (late onset), and 15 had AS in both surveys (persistent). Comparing the lung function parameters observed with the predicted by GLI only small differences were detected, except for FVC and FEF25–75, for which more than 5% of subjects had Z-score values beyond the Z-score normal limits. Furthermore, as well as did not significantly affect developmental changes in FVC and FEV1, the decrease in FEV1/FVC ratio was significantly higher in subjects with AS at the time of follow-up (late onset and persistent phenotypes) while the increase in FEF25–75 was significantly smaller in subjects with persistent AS (p < 0.05).ConclusionsThe GLI equations are valid in evaluating lung function during development, at least in terms of lung volume measurements. Findings also suggest that the FEF25–75 may be a useful tool for clinical and epidemiological studies of childhood asthma.

Broader criteria of undifferentiated connective tissue disease in idiopathic interstitial pneumonias

Kinder et al. proposed a broader definition of undifferentiated connective tissue disease (UCTD) and reported that the entity of nonspecific interstitial pneumonia (NSIP) is a lung manifestation of this more broadly defined UCTD. However, a retrospective study did not support their findings and its clinical significance remains unclear. We prospectively evaluated the significance of this broadly defined UCTD in idiopathic interstitial pneumonias (IIPs) in consecutive patients with surgical lung biopsy. Patients were evaluated with a symptoms check list and underwent comprehensive serologic testing as screening for UCTD. Clinical characteristics, high-resolution CT images, lung biopsy specimens, serial FVC change, and survival were analyzed. Among 76 patients with IIPs, 24 patients (32%) fulfilled the UCTD criteria. Diagnosis of 24 patients with UCTD was usual interstitial pneumonia in 12 (50%), NSIP in 7 (29%), and unclassifiable interstitial lung disease (ILD) in 5 (21%). The diagnosis of 52 patients who did not have UCTD was idiopathic pulmonary fibrosis in 27 (52%), NSIP in 11 (21%), unclassifiable ILD in 13 (25%) and cryptogenic organizing pneumonia in 1 (2%). One-year and two-year FVC changes showed no significant difference between UCTD and non-UCTD, however, significant differences in FVC change were observed among histopathological diagnoses both in UCTD and in non-UCTD. In multivariate survival analysis, %FVC and histopathological UIP pattern were independent predictors for survival but UCTD diagnosis was not. A diagnosis of UCTD was not useful in discriminating NSIP or in predicting disease progression and prognosis in our cohort of IIPs. Histopathological UIP pattern was an independent predictor for mortality irrespective of a diagnosis of UCTD.

Clinical features of primary ciliary dyskinesia in Cyprus with emphasis on lobectomized patients

Despite the manifestations of primary ciliary dyskinesia (PCD) in early life, the diagnosis is often much delayed. Since 1998 in Cyprus, we have established the only national diagnostic and clinical referral center for PCD. To review the phenotypic features at presentation of PCD patients in Cyprus in relation to age at diagnosis, with emphasis on previously lobectomised patients. The medical records of the diagnosed PCD patients were retrospectively reviewed to obtain clinical data on presentation. Thirty patients, aged 13.9 years (range 0.1, 58.4 years), were diagnosed with PCD. Twelve of them presented after the age of 18. The most common manifestations were chronic cough (100%), chronic rhinorrhea (96.7%), sputum production (92.9%), laterality defects (63.3%), a history of pneumonia (53.3%) and neonatal respiratory distress (50%). A history of lobectomy in the past was recorded in 16.7% (5 patients). Patients who presented in adulthood had significantly higher frequency of lobectomy (41.7% vs 0%, p-value = 0.006) and had more frequently low FEV1 (58.3% vs 0%, p-value = 0.015) than those who presented before. Serial measurements of FEV1 and FVC indicated significantly lower intercepts in lobectomised compared to the adult non-lobectomised patients both in terms of FEV1 (-4.90 vs -1.80, p-value = 0.022) and FVC (-5.43 vs -1.91, p-value = 0.029) z-score levels. Change in FEV1 and FVC across time was not statistically significant in either group. PCD often remains undiagnosed up to adulthood accompanied by appearance of advanced lung disease. Performance of lobectomies seems to be a poor prognostic factor for PCD in adulthood.

Effects of chest resistance exercise and chest expansion exercise on stroke patients' respiratory function and trunk control ability.

[Purpose] The purpose of this study was to examine the efficiency of chest resistance and chest expansion exercises for improving respiratory function and trunk control ability in patients with stroke. [Subjects] Forty patients with stroke were randomly allocated into a chest resistance exercise group (CREG, n = 20) and a chest expansion exercise group (CEEG, n = 20). [Methods] CREG patients underwent chest resistance exercises, and diaphragmatic resistance exercises by way of the proprioceptive neuromuscular facilitation. CEEG patients underwent respiratory exercises with chest expansion in various positions. Both groups received 30 minutes of training per day, five times per week, for eight weeks. [Results] Both the CERG and CEEG groups showed significant changes in FVC, FEV1, and TIS after the intervention. TIS was significantly increased in the CREG compared to the CEEG after the intervention. [Conclusion] Both chest resistance and chest expansion exercises were effective for improving respiratory function and trunk control ability in stroke patients; however, chest resistance exercise is more efficient for increasing trunk control ability.

Comparison of post operative pulmonary function between open surgeries and laparoscopies

Background: Respiratory function is depressed after abdominal surgery. Less trauma to the abdominal wall results in early postoperative recovery. Aim: The study was planned to compare recovery of postoperative respiratory functions between open surgeries and laparoscopic surgeries in the Indian population. Materials and Methods: 50 patients undergoing open surgery and 50 patients undergoing laparoscopy underwent tests on pulmonary functions (Forced Vital Capacity [FVC], Forced Expiratory Volume in first second [FEV1], Forced Expiratory Flow between 25% and 75% [FEF25%-75%]), Peak Expiratory Flow [PEF]and capillary blood gas analysis (paO2, paCO2) before surgery and after two days following surgery using RMS MEDSPIROR® and blood gas analysis of capillary blood. Results: Change in FVC, FEV1, FEF25%-75% , PEF, pO2 and pCO2 to 65.9%, 66.9%, 66%, 64.9%,92% and 99% respectively of the preoperative value following open surgery and to 82.5%, 84%, 86%, 82.5%,97.5% and 102% respectively of the preoperative value following laparoscopic surgery. Conclusions: Respiratory function recovery is better in laparoscopic surgery compared to open surgery.

Influence of Anti-TNF and Disease Modifying Antirheumatic Drugs Therapy on Pulmonary Forced Vital Capacity Associated to Ankylosing Spondylitis: A 2-Year Follow-Up Observational Study

Objective. To evaluate the effect of anti-TNF agents plus synthetic disease modifying antirheumatic drugs (DMARDs) versus DMARDs alone for ankylosing spondylitis (AS) with reduced pulmonary function vital capacity (FVC%). Methods. In an observational study, we included AS who had FVC% <80% at baseline. Twenty patients were taking DMARDs and 16 received anti-TNF + DMARDs. Outcome measures: changes in FVC%, BASDAI, BASFI, 6-minute walk test (6MWT), Borg scale after 6MWT, and St. George's Respiratory Questionnaire at 24 months. Results. Both DMARDs and anti-TNF + DMARDs groups had similar baseline values in FVC%. Significant improvement was achieved with anti-TNF + DMARDs in FVC%, at 24 months, when compared to DMARDs alone (P = 0.04). Similarly, patients in anti-TNF + DMARDs group had greater improvement in BASDAI, BASFI, Borg scale, and 6MWT when compared to DMARDs alone. After 2 years of follow-up, 14/16 (87.5%) in the anti-TNF + DMARDs group achieved the primary outcome: FVC% ≥80%, compared with 11/20 (55%) in the DMARDs group (P = 0.04). Conclusions. Patients with anti-TNF + DMARDs had a greater improvement in FVC% and cardiopulmonary scales at 24 months compared with DMARDs. This preliminary study supports the fact that anti-TNF agents may offer additional benefits compared to DMARDs in patients with AS who have reduced FVC%.

Advantages of CyberKnife for inoperable stage I peripheral non-small-cell lung cancer compared to three-dimensional conformal radiotherapy.

This study was conducted to compare the clinical curative effect and acute radiation lung reactions between CyberKnife (CK) and three-dimensional conformal radiotherapy (3DCRT) treatment for inoperable stage I peripheral non-small-cell lung cancer (NSCLC). We retrospectively analyzed 68 patients with inoperable stage I peripheral NSCLC between 2012 and 2013 in our institution. The CK patients were treated with 42-60 Gy in three fractions, while the 3DCRT patients were treated with a total of 60 Gy, at 2 Gy per fraction. The patients were followed up and the clinical outcome was evaluated according to the Response Evaluation Criteria in Solid Tumours. We assessed the presence of acute radiation pneumonitis and pulmonary function status by thoracic scan and pulmonary function tests following CK and 3DCRT treatment. The binary univariate logistic regression analysis demonstrated that treatment method and forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC) prior to treatment (pre-FEV1/FVC) were the main factors affecting the risk of radiation pneumonitis. The analysis of these factors through multivariate logistic regression method demonstrated that treatment method for grade 1 and 2 [odds ratio (OR)= 7.866 and 11.334, respectively) and pre-FEV1/FVC for grade 1, 2 and 3 (OR = 5.062, 11.498 and 15.042, respectively) were significant factors affecting the risk of radiation pneumonitis (P<0.05). The 68 patients were divided into two subgroups using the threshold of pre-FEV1/FVC selected by the receiver operating characteristic curve. There were significant differences between the 3DCRT and CK treatment in both the pre-FEV1/FVC <68% and ≥68% subgroups for radiation pneumonitis (P=0.023 and 0.002, respectively). There was no statistically significant change in FVC, FEV1 and carbon monoxide diffusion capacity (DCLO) in the CK group, whereas there was a decrease in DCLO in the 3DCRT group. The complete remission rate was 40 vs. 34.2% at 1 year in the CK and 3DCRT groups, respectively. In conclusion, in this cohort of patients with inoperable stage I peripheral NSCLC, CK appears to be a safe and superior alternative to conventionally fractionated radiotherapy.

S8 Rituximab Therapy For Refractory Myositis Related Interstitial Lung Disease Unresponsive To Conventional Immunosuppression: The Bristol Interstitial Lung Disease Service Experience

Introduction Rituximab is a chimeric monoclonal antibody against CD20 that depletes B-lymphocytes. There is increasing evidence for its use in Scleroderma ILD. 1 Recently it has been reported as rescue therapy in patients with connective tissue disease related severe fibrotic lung disease who have failed conventional immunosuppression. 2 It remains unclear which patients are most likely to benefit from this potent immunosuppressive treatment. We review here the experience of the Bristol Interstitial Lung Disease service in use of Rituximab in a subset of patients with myositis (Anti-synthetase syndrome and Dermatomyositis). Methods We retrospectively reviewed the case notes of 10 patients with severe and progressive ILD despite immunosuppression with Cyclophosphamide and Mycophenolate Mofetil, who had received salvage treatment with Rituximab. Serial pulmonary function tests, 6 min walk distances and HRCT appearances (as assessed by a Thoracic radiologist) were compared in the year before and after Rixtuximab therapy. Changes in physiological variables compared to nadir at treatment were compared with paired-samples T-Test. Results The average age of the patients was 49.8 (range 26.9–72.99), with 7/10 female. 4 patients had dermatomyositis, while 6 had Anti-Synthetase Syndrome (2 Anti-Jo1, 2 Anti-PL12, 1 Anti-PL7, 1 Anti-PM-Scl). There were complete lung function data available for 9 patients and 6MWD data for 6 patients. CT appearances stabilised in all 9 patients with follow-up scans available, with significant improvement in 2 (1 after a second pulse of Rituximab). FVC improved after treatment by an average of 9.2% (p = 0.023, 95% CI 1.67–16.76), with TLCO improving by an average of 6.1% (NS). Figure shows% change in FVC and TLCO leading to and after therapy. 6MWD remained stable. There were no adverse events reported. Summary Our experience adds to the growing evidence to support the use of Rituximab in severe CTD-ILD, and suggests that a subset of patients with myositis may show good therapeutic response. References Daoussis et al . Rheumatology .2010;49;271–80 Keir et al . Respirology 2013;19;353–9

Small changes in lung function in runners with marathon-induced interstitial lung edema

The purpose of this study was to assess lung function in runners with marathon‐induced lung edema. Thirty‐six (24 males) healthy subjects, 34 (SD 9) years old, body mass index 23.7 (2.6) kg/m2 had posterior/anterior (PA) radiographs taken 1 day before and 21 (6) minutes post marathon finish. Pulmonary function was performed 1–3 weeks before and 73 (27) minutes post finish. The PA radiographs were viewed together, as a set, and evaluated by two experienced readers separately who were blinded as to time the images were obtained. Radiographs were scored for edema based on four different radiological characteristics such that the summed scores for any runner could range from 0 (no edema) to a maximum of 8 (severe interstitial edema). Overall, the mean edema score increased significantly from 0.2 to 1.0 units (P <0.01), and from 0.0 to 2.9 units post exercise in the six subjects that were edema positive (P = 0.03). Despite a 2% decrease in forced vital capacity (FVC, P =0.024) and a 12% decrease in alveolar‐membrane diffusing capacity for carbon monoxide (DmCO, P =0.01), there was no relation between the change in the edema score and the change in DmCO or FVC. In conclusion, (1) mild pulmonary edema occurs in at least 17% of subjects and that changes in pulmonary function cannot predict the occurrence or severity of edema, (2) lung edema is of minimal physiological significance as marathon performance is unaffected, exercise‐induced arterial hypoxemia is unlikely, and postexercise pulmonary function changes are mild.

Sodium channel blockers for cystic fibrosis.

People with cystic fibrosis (CF) have increased transport of the salt, sodium across their airway lining. Over-absorption of sodium results in the dehydration of the liquid that lines the airway surface and (along with defective chloride secretion) is a primary defect in people with CF. To determine whether the topical administration of drugs that block sodium transport improves the respiratory condition of people with CF. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We contacted principal investigators known to work in the field, previous authors and pharmaceutical companies who manufacture ion transport agents for unpublished or follow-up data.Most recent search of the Group's register: 19 December 2013. Published or unpublished randomised controlled trials (RCTs) or quasi-randomised controlled trials of sodium channel blockers compared to placebo or another sodium channel blocker or the same sodium channel blocker at a different dosing regimen. Two authors independently extracted data. Meta-analysis was limited due to differing study designs. Five RCTs, with a total of 226 participants, examining the topical administration of the short-acting sodium channel blocker, amiloride, compared to placebo were identified as eligible for inclusion in the review. In three studies over six months, there was a significant difference found in the difference in relative change in FVC in favour of placebo (weighted mean difference 1.51% (95% confidence interval -2.77 to -0.25), although heterogeneity was evident. A two-week study demonstrated that hypertonic saline with amiloride pre-treatment did not result in a significant improvement in respiratory function or mucus clearance, in contrast to pre-treatment with placebo. There were no significant differences identified in other clinically relevant outcomes. We found no evidence that the topical administration of a short-acting sodium channel blocker improves respiratory condition in people with cystic fibrosis and some limited evidence of deterioration in lung function.

Anterior Mediastinal Fat Changes in Idiopathic Pulmonary Fibrosis: A Preliminary Study

Background: The mediastinum is composed primarily of fatty tissue that is surrounded by the lungs bilaterally. There is a lack in the published literature in studying changes in mediastinal fat in idiopathic pulmonary fibrosis (IPF). The purpose of this study was to determine whether the shape and dimensions of the anterior mediastinal fat in patients with IPF are different from that of a normal control group and to correlate the changes with disease severity. Design and Setting: This prospective case control study was done at the chest department of Assiut University Hospital on IPF patients from May 2010-September 2012. A questionnaire containing questions such as age, sex, clinical findings, high resolution computerized tomography (HRCT) score and pulmonary function tests (PFTs) was filled for patients and normal controls. Results: The IPF retrosternal AP dimension was significantly shorter (p = 0.03) and the transverse dimension was longer (p = 0.001) than that in the normal control group. The convex shape of the anterior mediastinum was predictive of IPF (p = 0.001), whereas concave shape was predictive of normal controls (p = 0.001). The change in anteroposterior diameter (AP) and transverse diameters showed significant correlation with the changes in FVC, DLCO and HRCT score. Conclusions: IPF patients had reduced retrosternal AP and increased transverse dimensions than those of the controls with convex shape of their anterior mediastinal fat. Changes in anterior mediastinal fat dimensions are correlated with lower FVC, DLCO and higher HRCT score. A larger sample size, better multicenteric study is needed to confirm the results of this study.

The potential additional benefit of infliximab in patients with chronic pulmonary sarcoidosis already receiving corticosteroids: A retrospective analysis from a randomized clinical trial

Infliximab, a TNF-alpha antagonist, has shown efficacy in the treatment of sarcoidosis. Since corticosteroids inhibit TNF-alpha expression, we postulated that sarcoidosis patients receiving a sufficient corticosteroid dose may have an attenuated response to the addition of infliximab. We analyzed data from a previous randomized double blind prospective trial of infliximab versus placebo for chronic pulmonary sarcoidosis. The effect of the maintenance corticosteroid dose on the change in FVC % predicted between 0 and 24 weeks (ΔFVC%pred0-24) was analyzed in two ways. First, the mean ΔFVC%pred0-24 was calculated for the placebo and infliximab groups using three different daily prednisone equivalent dose thresholds: a) <10mg versus ≥10mg; b) <15mg versus ≥15mg; c) <20mg versus ≥20mg. Second, in both the placebo and infliximab groups, a correlation coefficient was calculated between the maintenance corticosteroid dose and ΔFVC%pred0-24. Both the group that received infliximab and either a maintenance daily dose of <10mg of prednisone and the group receiving ≥10mg had a significant increase in FVC%pred0-24. However, both the groups that received infliximab and a corticosteroid dose of >15mg of prednisone and ≥20mg of prednisone did not demonstrate a significant ΔFVC%pred0-24. For the placebo group, there was no significant correlation between the corticosteroid dose and the ΔFVC%pred0-24. For the infliximab group, there was a significant correlation (p=0.0097) between higher corticosteroid dose and less improvement in FVC%pred0-24. Our results suggest that infliximab adds minimal potential benefit to corticosteroids for pulmonary sarcoidosis at doses above 15-20mg/day of prednisone.

P81 Long-term effect of combined anterior and posterior spinal fusion on pulmonary function and quality of life in young people with adolescent idiopathic scoliosis

BackgroundThe deleterious effects of progressive adolescent idiopathic scoliosis (AIS) on lung function and quality of life are cause for concern. Although surgical correction of AIS aims to halt progression of...

Two-Year Follow-up in Patients Treated With Emphysematous Lung Sealant for Advanced Emphysema

Endoscopic lung volume-reduction therapy for emphysema has been associated with therapeutic responses smaller in magnitude and less durable than surgical volume reduction (LVRS). Bronchoscopic emphysematous lung sealant (ELS) therapy has been shown to produce improvements in pulmonary function similar to surgery at 1 year. This case series summarizes safety and efficacy data of all patients from the initial ELS study out to 2 years. Between 1 and 2 years, there were three all-cause adverse events requiring hospitalization. One patient went on to successful lung transplant. Improvements relative to baseline in spirometry (change in FEV1: + 14.3 ± 33.1%; change in FVC: + 5.8 ± 23.2%) and diffusing capacity (change in diffusing capacity of the lung for carbon monoxide: + 10.6 ± 20.6%) were observed at 2 years. An exponential model fit to FEV₁ data at 6, 12, 18, and 24 months predicted improvements from a baseline of > 5% out to 4.1 years, similar to what has been reported following surgery. This report confirms long-term safety and efficacy following ELS therapy in advanced emphysema. Studies in a larger cohort are needed to define the role of ELS therapy in the treatment algorithm of patients with this condition.