Restrictive Lung Function Research Articles

MiR-29b supplementation decreases expression of matrix proteins and improves alveolarization in mice exposed to maternal inflammation and neonatal hyperoxia.

Even with advances in the care of preterm infants, chronic lung disease or bronchopulmonary dysplasia (BPD) continues to be a significant pulmonary complication. Among those diagnosed with BPD, a subset of infants develop severe BPD with disproportionate pulmonary morbidities. In addition to decreased alveolarization, these infants develop obstructive and/or restrictive lung function due to increases in or dysregulation of extracellular matrix proteins. Analyses of plasma obtained from preterm infants during the first week of life indicate that circulating miR-29b is suppressed in infants that subsequently develop BPD and that decreased circulating miR-29b is inversely correlated with BPD severity. Our mouse model mimics the pathophysiology observed in infants with severe BPD, and we have previously reported decreased pulmonary miR-29b expression in this model. The current studies tested the hypothesis that adeno-associated 9 (AAV9)-mediated restoration of miR-29b in the developing lung will improve lung alveolarization and minimize the deleterious changes in matrix deposition. Pregnant C3H/HeN mice received an intraperitoneal LPS injection on embryonic day 16 and newborn pups were exposed to 85% oxygen from birth to 14 days of life. On postnatal day 3, AAV9-miR-29b or AAV9-control was administered intranasally. Mouse lung tissues were then analyzed for changes in miR-29 expression, alveolarization, and matrix protein levels and localization. Although only modest improvements in alveolarization were detected in the AAV9-miR29b-treated mice at postnatal day 28, treatment completely attenuated defects in matrix protein expression and localization. Our data suggest that miR-29b restoration may be one component of a novel therapeutic strategy to treat or prevent severe BPD in prematurely born infants.

Pulmonary function of automobile repair workers in the informal sector of Raichur urban

Background: Automobile repair workers of the informal sector are exposed to dusts, toxic fumes and aerosols. Long term occupational exposure may lead to pulmonary function impairment. Hence, the objectives were to study the occurrence of obstructive and restrictive pulmonary impairment among the automobile repair workers by using pulmonary function test and the factors associated with it.Methods: A cross sectional study was carried out in automobile repair workers who work in informal sector in the urban area of Raichur in Karnataka. The pulmonary function tests viz. Forced Expiratory volume in one second, Forced vital capacity, Peak Expiratory Flow Rate per liter and FEV1/FVC ratio in percentage were measured for each worker in sitting posture using a digital spirometer. Data collected were analyzed in SPSS 16.0 software. Chi-square test and t test was used.Results: Out of the 97 automobile repair workers, 42 (43.3%) had normal pulmonary function. Among the abnormal PFT, 20 (20.6%) had obstructive lung function, 25 (25.8%) had restrictive lung function and 10 (10.3%) had mixed obstructive and restrictive lung function. The workers with abnormal PFT consisted of body repair workers (25.0%), mechanical workers (38.1%), spray painters (75.0%), battery repair workers (100.0%) and tyre retreading workers (88.9%).Conclusions: In this study, 56.7% of workers had some form of pulmonary function impairment. Smoking, increase in duration of work hours and years of work showed significant pulmonary impairment. The study highlights the need for creating awareness and encouraging the use of protective gears such as masks, early screening, diagnosis and treatment of respiratory diseases among the garage workers.

AAV9‐miR‐29b Treatment Decreases Expression of Matrix Proteins and Improves Alveolarization in Mice Exposed to Maternal Inflammation and Neonatal Hyperoxia

BackgroundBronchopulmonary dysplasia (BPD) continues to be a significant pulmonary complication for preterm infants. Severe BPD is characterized by decreased alveolarization and obstructive and/or restrictive lung function due to increases in or dysregulation of extracellular matrix proteins. We have previously reported decreased pulmonary miR‐29b expression in our mouse model that mimics the pathophysiology observed in infants with severe BPD. The current studies tested the hypothesis that AAV9‐mediated restoration of miR‐29b in the developing lung will improve lung alveolarization and minimize the pulmonary fibrosis.MethodsPregnant C3H/HeN mice received an intraperitoneal LPS injection on E16 and newborn pups were exposed in 85% oxygen from birth to 14 days of life. On postnatal day 3, PBS containing adeno‐associated 9 (AAV9)‐mir‐29b or AAV9‐control was administered intranasally. On postnatal day 14 or 28, mouse lung tissues were analyzed for changes in miR‐29 expression, alveolarization, and matrix protein expression.ResultsDecreases in alveolarization and increases in septal thickness were observed at both 14 and 28 days after LPS/O2 exposure. Administration of AAV9‐miR29b modestly improved alveolarization at 28 days but completely prevented the increases in septal thickness observed at both 14 and 28 days. AAV9‐miR29b also prevented the increases in phospho‐SMAD2/3, aSMA, vimentin, and MMP‐9.ConclusionOur data suggest that miR‐29b restoration may represent a novel therapeutic strategy to treat or prevent severe BPD in prematurely born infants.

Liposomal miR‐29b Delivery Attenuates Increased Expression of Matrix Proteins and Improves Alveolarization in Mice Exposed to Maternal Inflammation and Neonatal Hyperoxia

BackgroundChronic lung disease or bronchopulmonary dysplasia (BPD) continues to be a significant pulmonary complication for preterm infants. In addition to decreased alveolarization, these infants can develop obstructive and/or restrictive lung function due to increases in or dysregulation of extracellular matrix proteins. Our mouse model mimics the pathophysiology observed in infants with severe BPD and we have previously reported decreased pulmonary miR‐29b expression in this model. The current studies tested the hypothesis that liposomal mediated restoration of miR‐29b in the developing lung will improve lung alveolarization and minimize the pulmonary fibrosis.MethodsMiR‐29 levels were measured in the plasma of preterm infants by PCR. Pregnant C3H/HeN mice received an intraperitoneal LPS injection on E16 and newborn pups were exposed in 85% oxygen from birth to 14 days of life. On postnatal day 3, PBS containing a liposomal preparation of miR‐29b or an empty liposome was administered intranasally. On postnatal day 14 or 28, mouse lung tissues were analyzed for changes in miR‐29 expression, alveolarization, and matrix protein expression.ResultsAnalyses of plasma obtained from preterm infants during the first week of life indicate that circulating miR‐29b levels are suppressed and the levels are inversely correlated to severity in infants later diagnosed with BPD. In our mouse model, modest improvements in alveolarization were detected in the miR‐29b‐treated mice. MiR‐29b treatment completely attenuated the LPS/O2‐associated increases in aSMA, MMP‐9, and SMAD 2/3 and restored PDGFa levels in lung tissues.ConclusionOur data suggest that miR‐29b restoration may represent a novel therapeutic strategy to treat or prevent severe BPD in prematurely born infants.

Impact of airflow limitation in chronic heart failure.

BackgroundComorbidities are common in chronic heart failure (HF) patients, but diagnoses are often not based on objective testing. Chronic obstructive pulmonary disease (COPD) is an important comorbidity and often neglected because of shared symptoms and risk factors. Precise prevalence and consequences are not well known. Therefore, we investigated prevalence, pulmonary treatment, symptoms and quality of life (QOL) of COPD in patients with chronic HF.Methods205 patients with stable HF for at least 1 month, aged above 50 years, were included from our outpatient cardiology clinic, irrespective of left ventricular ejection fraction. Patients performed post-bronchodilator spirometry, a six-minute walk test (6-MWT) and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). COPD was diagnosed according to GOLD criteria. Restrictive lung function was defined as FEV1/FVC ≥0.70 and FVC <80% of predicted value. The BODE and ADO index, risk scores in COPD patients, were calculated.ResultsAlmost 40% fulfilled the criteria of COPD and 7% had restrictive lung disease, the latter being excluded from further analysis. Noteworthy, 63% of the COPD patients were undiagnosed and 8% of those without COPD used inhalation therapy. Patients with COPD had more shortness of breath despite little difference in HF severity and similar other comorbidities. KCCQ was significantly worse in COPD patients. The ADO and BODE indices were significantly different.ConclusionCOPD is very common in unselected HF patients. It was often not diagnosed and many patients received treatment without being diagnosed with COPD. Presence of COPD worsens symptoms and negatively effects cardiac specific QOL.

Influence of the Sternum Mobilization Technique on the Spirometry Data

Introduction. Alteration of the mobility of the sternum, decrease of the external respiration functions are most often due to two groups of diseases: chronic obstructive lung disease and degenerative dystrophic diseases of the spinal column. Patients presenting degenerative dystrophic lesion of the spinal column often address to osteopaths and manual therapists. It is important to justify the most effective method of osteopathic correction in treatment of this type of patients.Research objectives. To evaluate the effectiveness of the sternum mobilization technique according to the lung capacity indices, peakfluorometric index, chest excursion.Research methods. Patients aged from 20 to 45 took part in the research. They were divided into two groups regardless of sex. There were 15 people in each group. All the patients had regional biomechanical disorder of the sternum from 1 to 3 points with predominant structural constituent and all of them complained of discomfort in the thoracic region. Osteopathic correction of patients from the first (experimental) group included sternum mobilization technique with the use of the recoil methods during the first and the second consultation. In the control group the sternum mobilization techniques were not realized. The evaluation of the treatment results was held on the basis of the analysis of the spirometry data. Indices of the chest excursion, lung capacity and peakfluorometric index were evaluated.Results. It was proven that the sternum mobilization technique is effective and demonstratively increases lung capacity and peakfluorometric index. At the same time the sternum mobilization technique is not effective in respect of the chest excursion volume.Conclusion. Sternum mobilization technique can be recommended for using in osteopathy and manual therapy in order to improve the restrictive lung function.

Mechanisms of Effort Intolerance in Patients With Rheumatic Mitral Stenosis: Combined Echocardiography and Cardiopulmonary Stress Protocol

ObjectivesThis study sought to evaluate mechanisms of effort intolerance in patients with rheumatic mitral stenosis (MS). BackgroundCombined stress echocardiography and cardiopulmonary testing allows assessment of cardiac function, hemodynamics, and oxygen extraction (A–Vo2 difference). MethodsUsing semirecumbent bicycle exercise, 20 patients with rheumatic MS (valve area 1.36 ± 0.4 cm2) were compared to 20 control subjects at 4 pre-defined activity stages (rest, unloaded, anaerobic threshold, and peak). Various echocardiographic parameters (left ventricular volumes, ejection fraction, stroke volume, mitral valve gradient, mitral valve area, tissue s′ and e′) and ventilatory parameters (peak oxygen consumption [Vo2] and A–Vo2 difference) were measured during 8 to 12 min of graded exercise. ResultsComparing patients with MS to control subjects, significant differences (both between groups and for group by time interaction) were seen in multiple parameters (heart rate, stroke volume, end-diastolic volume, ejection fraction, s′, e′, Vo2, and tidal volume). Exercise responses were all attenuated compared to control subjects. Comparing patients with MS and poor exercise tolerance (<80% of expected) to other subjects with MS, we found attenuated increases in tidal volume (p = 0.0003), heart rate (p = 0.0009), and mitral area (p = 0.04) in the poor exercise tolerance group. These patients also displayed different end-diastolic volume behavior over time (group by time interaction p = 0.05). In multivariable analysis, peak heart rate response (p = 0.01), tidal volume response (p = 0.0001), and peak A–Vo2 difference (p = 0.03) were the only independent predictors of exercise capacity in patients with MS; systolic pulmonary pressure, mitral valve gradient, and mitral valve area were not. ConclusionsIn patients with rheumatic MS, exercise intolerance is predominantly the result of restrictive lung function, chronotropic incompetence, limited stroke volume reserve, and peripheral factors, and not simply impaired valvular function. Combined stress echocardiography and cardiopulmonary testing can be helpful in determining mechanisms of exercise intolerance in patients with MS.

Restrictive spirometric pattern in the general adult population: Methods of defining the condition and consequences on prevalence

BackgroundAttempts have been made to use dynamic spirometry to define restrictive lung function, but the definition of a restrictive spirometric pattern (RSP) varies between studies such as BOLD and NHANES. The aim of this study was to estimate the prevalence and risk factors of RSP among adults in northern Sweden based on different definitions. MethodsIn 2008–2009 a general population sample aged 21–86y within the obstructive lung disease in northern Sweden (OLIN) studies was examined by structured interview and spirometry, and 726 subjects participated (71% of invited). The prevalence of RSP was calculated according to three different definitions based on pre-as well as post-bronchodilator spirometry:1) FVC < 80% & FEV1/FVC > 0.72) FVC < 80% & FEV1/FVC > LLN3) FVC < LLN & FEV1/FVC > LLN ResultsThe three definitions yielded RSP prevalence estimates of 10.5%, 11.2% and 9.4% respectively, when based on pre-bronchodilator values. The prevalence was lower when based on post-bronchodilator values, i.e. 7.3%, 7.9% and 6.6%. According to definition 1 and 2, the RSP prevalence increased by age, but not according to definition 3. The overlap between the definitions was substantial. When corrected for confounding factors, manual work in industry and diabetes with obesity were independently associated with an increased risk for RSP regardless of definition. ConclusionsThe prevalence of RSP was 7–11%. The prevalence estimates differed more depending on the choice of pre- compared to post-bronchodilator values than on the choice of RSP definition. RSP was, regardless of definition, independently associated with manual work in industry and diabetes with obesity.

Comparison of pulmonary functions of thalassemic and of healthy children

Objectives The aim of this study was to compare some pulmo-nary functions of thalassemic patients and those of normal chil-dren. Factors correlated with lung dysfunction were assessed.Methods This cross-sectional study compared some pulmonaryfunctions of thalassemic patients with those of healthy children.The study was performed in the Department of Child Health, CiptoMangunkusumo Hospital, Jakarta, Indonesia. Pre- and post-trans-fusion hemoglobin levels of the thalassemic subjects were deter-mined. Other data such as chelation therapy and serum ferritinlevels were also obtained. Both thalassemic and control subjectsunderwent routine physical examinations and lung function testsusing an electronic spirometer. Spirometry was repeated threetimes for each subject, and only the best result was recorded.Results Sixty-three thalassemic patients were enrolled, consist-ing of 32 male and 31 female subjects. Healthy subjects consistedof 31 males and 31 females. Most thalassemic patients (46/63)were found to have lung function abnormalities. This was signifi-cantly different from control subjects, of whom most (39/62) hadnormal lung function. Restrictive lung function abnormality was themost common (42/63) observation documented. Serum ferritin lev-els were obtained from 28 male and 29 female thalassemic sub-jects. There was no correlation between percentage from predictedforced vital capacity and serum ferritin levels, whether in male(r=0.191; P=0.967) or female (r =-0.076, P=0.695) thalassemicsubjects.Conclusion Thalassemic patients have significantly lower lungfunction than healthy children. More thalassemic patients had lungfunction abnormalities compared to healthy children. Restrictivedysfunction was the most common finding in the thalassemic group.No correlation was found between lung function and serum ferritinlevels

O5-2 - Restrictive Lung Function is Associated with Increased Sympathetic Nerve Activity in Patients with Heart Failure

O5-2 - Restrictive Lung Function is Associated with Increased Sympathetic Nerve Activity in Patients with Heart Failure

Pattern of Lung Function Is Not Associated with Prior or Future Morbidity in Children with Sickle Cell Anemia.

Patient factors associated with development of abnormal lung function in children with sickle cell anemia (SCA) have not been fully characterized. To characterize lung function abnormalities among children with SCA and to determine whether these steady-state lung function results were associated with morbidity before or after testing among children with SCA. This study was part of the prospective National Institutes of Health-funded Sleep and Asthma Cohort Study. Children with HbSS or Hb Sβ(o) (SCA) were enrolled without regard for sickle cell-related comorbidities or diagnosis of asthma. Lung function was measured by spirometry and plethysmography on the same day, when free of acute disease. Standardized asthma symptom questionnaires and review of the medical records were also performed. A total of 149 children aged 6 to 19 years completed lung function testing, of whom 139 participants had retrospective morbidity data from birth to the test date, and 136 participants were followed prospectively for a median of 4.3 years from the test date. At baseline, percentages with normal, obstructive, restrictive, nonspecific, and mixed lung function patterns were 70, 16, 7, 6, and 1, respectively. Neither retrospective rates of pain nor acute chest syndrome was associated with lung function patterns. Furthermore, baseline lung function pattern was not predictive of future pain or acute chest syndrome episodes. The majority of children with SCA have lung function that is within the normal range. Abnormal lung function patterns were not associated with prior vasoocclusive pain or acute chest syndrome episodes, and baseline lung function patterns did not predict future vasoocclusive pain or chest syndrome episodes.

Clinical Predictors of a Diagnosis of Common Variable Immunodeficiency-related Granulomatous-Lymphocytic Interstitial Lung Disease.

Granulomatous-lymphocytic interstitial lung disease (GLILD) has emerged as a major cause of morbidity in patients with common variable immunodeficiency (CVID). While GLILD is among the most serious noninfectious pulmonary complications of CVID, risk factors for this condition have not been reported. To identify clinical, physiologic, and serologic risk factors for GLILD in adults with CVID. Of 345 consecutive adult patients with CVID, we identified 34 in the National Jewish Health research database who had a radiographic-pathologic diagnosis of GLILD evaluated between 2002 and 2014. Each case was age and sex matched to 52 CVID control subjects. We used logistic regression to determine independent predictors of GLILD. A mixed effects model was used to estimate the longitudinal change in percent predicted FVC. The mean time from CVID diagnosis to GLILD detection was 7.8 years. Compared with matched control subjects, cases were more likely to have a history of autoimmune cytopenia, hypersplenism, polyarthritis, lower marginal zone and switched memory B cells, and restrictive lung function. Multivariate analysis revealed that hypersplenism (odds ratio [OR], 24; 95% confidence interval [CI], 4.5-179.1), polyarthritis (OR, 19; 95% CI, 2.3-206.8), and percent predicted FVC (OR, 0.93; 95% CI, 0.87-0.98) were independently associated with the development of GLILD. The rate of change of percent predicted FVC (slope, P = 0.48) did not vary significantly in patients with GLILD over a mean follow-up of 7 years after diagnosis. Hypersplenism and polyarthritis are strong risk factors for GLILD in patients with CVID. Percent predicted FVC remained stable over time in patients with GLILD.

Parenchymal lung involvement in adult-onset Still disease: A STROBE-compliant case series and literature review.

Parenchymal lung involvement (PLI) in adult-onset Still's disease (AOSD) has seldom, if ever, been studied. We examine here retrospective cohort AOSD cases and present a review of the literature (1971–2014) on AOSD-related PLI cases.Patients with PLI were identified in 57 AOSD cases. For inclusion, the patients had to fulfill Yamaguchi or Fautrel classification criteria, show respiratory symptoms, and have imaging evidence of pulmonary involvement, and data allowing exclusion of infectious, cardiogenic, toxic, or iatrogenic cause of PLI should be available. This AOSD + PLI group was compared with a control group (non–PLI-complicated AOSD cases from the same cohort).AOSD + PLI was found in 3 out of the 57 patients with AOSD (5.3%) and the literature mentioned 27 patients. Among these 30 AOSD + PLI cases, 12 presented an acute respiratory distress syndrome (ARDS) and the remaining 18 another PLI. In the latter, a nonspecific interstitial pneumonia computed tomography pattern prevailed in the lower lobes, pulmonary function tests showed a restrictive lung function, the alveolar differential cell count was neutrophilic in half of the cases, and the histological findings were consistent with bronchiolitis and nonspecific interstitial pneumonia. Corticosteroids were fully efficient in all but 3 patients. Ten out of 12 ARDS cases occurred during the first year of the disease course. All ARDS-complicated AOSD cases received corticosteroids with favorable outcomes in 10 (2 deceased). Most PLIs occurred during the systemic onset of AOSD.PLI may occur in 5% of AOSDs, of which ARDS is the most severe. Very often, corticosteroids are efficient in controlling this complication.

Restrictive Lung Function Is Related to Sympathetic Hyperactivity in Patients With Heart Failure

BackgroundSympathoexcitation and impaired lung function are common in patients with severe heart failure (HF). However, the association between impaired lung function and sympathoexcitation remains unknown. Methods and ResultsMuscle sympathetic nerve activity (MSNA) and clinical variables were determined in 83 HF patients with left ventricular ejection fraction (LVEF) <0.45. Restrictive and obstructive changes on spirometry were defined as reduced forced vital capacity (FVC) of <80% of predicted and a ratio of forced expiratory volume in the first second to FVC of <70%, respectively. Restrictive and obstructive changes were identified in 17 and 21 patients, respectively. MSNA was higher in patients with restrictive changes than in those without restrictive changes (84 vs 66 bursts per 100 beats; P < .01), but was similar in those with and without obstructive changes. Univariate analyses showed that FVC, estimated glomerular filtration rate (eGFR), specific activity scale, B-type natriuretic peptide level, LVEF, age, and use of aldosterone receptor blockers were significant predictors of MSNA burst incidence. Multivariate analysis revealed that FVC, LVEF, and eGFR were independent factors for increased burst incidence. Changes in FVC during follow-up negatively correlated with changes in burst rate (n = 11; P < .01). ConclusionRestrictive lung function was associated with increased sympathetic nerve activity independently from HF severity.

Obstructive and Restrictive Lung Function Measures and CKD: National Health and Nutrition Examination Survey (NHANES) 2007-2012.

Prevalence and factors associated with obstructive and restrictive lung function in people with chronic kidney disease (CKD) are unknown. Cross-sectional and longitudinal analyses. Participants aged 40 to 79 years from NHANES (National Health and Nutrition Examination Survey) 2007 to 2012 who underwent spirometry testing. CKD (estimated glomerular filtration rate [eGFR] >15-<60mL/min/1.73m(2) or urinary albumin-creatinine ratio≥ 30mg/g). Restrictive lung function (defined as FEV1/FVC≥0.70 and baseline FVC<80% predicted), obstructive lung function (defined as FEV1/FVC<0.70 based on postbronchodilator spirometric results), and mortality data (available for 2007-2008 and 2009-2010 survey periods). 7,610 participants (CKD=1,338; non-CKD=6,272) were included. Prevalences of obstructive lung function adjusted to the mean age of 55 years and 50% men in the CKD and non-CKD groups were 15.6% and 13.3%, respectively (P=0.2). Similarly, adjusted prevalences of restrictive lung function in the CKD and non-CKD groups were 9.8% and 6.7%, respectively (P=0.01). Presence of albumin-creatinine ratio ≥ 30mg/g was associated with obstructive (OR, 1.42; 95% CI, 1.07-1.88) and restrictive lung function (OR, 1.43; 95% CI, 1.01-2.03) in the entire study cohort. eGFR<60mL/min/1.73m(2) was associated with higher odds of obstructive lung function. In a multivariable Cox model, age (HR, 1.07; 95% CI, 1.04-1.11) and presence of obstructive lung function (HR, 2.68; 95% CI, 1.80-3.97), but not CKD measures, were associated with death. Small proportion of participants with advanced kidney disease. In a representative sample of US adults, impaired lung function is common in those with and without CKD. Albuminuria was independently associated with both obstructive and restrictive lung function, and eGFR<60mL/min/1.73m(2) was associated with higher odds of obstructive lung function. Older age and obstructive lung function were associated with higher likelihood of death. Further studies examining the burden of lung disease in advanced CKD are needed.

The relationship between serum fatty-acid binding protein 4 level and lung function in Korean subjects with normal ventilatory function.

BackgroundThe aim of this study was to assess the association of lung function with serum fatty-acid binding protein 4 (FABP4) in apparently healthy Korean adults.MethodsIn 495 participants in a health screening program, Force Exploratory Volume (FEV) 1 and Forced Vital Capacity (FVC) were assessed with standard spirometry. Subjects with obstructive (n = 19) and restrictive (n = 45) lung function were excluded from the analysis. Serum FABP4 level was measured by enzyme-linked immunosorbent assay and transformed into Ln(FABP4). 431 subjects with normal ventilator function (72.4 % men, mean age 41 years) were included in the final analysis.ResultsMean Ln(FABP4) significantly decreased in subjects from 1st quartile to 4th quartile of FVC (p = 0.008). Ln(FABP4) did not show significant differences across the quartile groups of FEV1. The odds ratio (OR) of being in the lowest quartile of FVC was 2.704 in subject with 3rd tertile of Ln(FABP4) after full adjustment for confounding variables {95 % confidence interval (CI) 1.397 ~ 5.357}. OR of being in the lowest quartile of FEV1 was 1.822 (95 % CI 1.021 ~ 3.298) in subjects with 3rd tertile of Ln(FABP4) after adjustment of age and sex, which was attenuated after full adjustment for confounding variables.ConclusionIncreased FABP4 level showed increased risk for reduced lung function in subjects with normal ventilatory function.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-016-0190-8) contains supplementary material, which is available to authorized users.

Lung Function in Patients with Congenital Heart Disease: Prevalence, Severity, and Correlation to Diagnosis

Objectives: Since restrictive lung function is an independent predictor of mortality (1) in congenital heart disease (CHD), evaluation of lung function in patients with CHD should be performed as part of the follow-up routine; analysis includes description of prevalence, type of lung disease and severity and its correlation with the underlying diagnosis.

Mild Lung Restriction in Breast Cancer Patients After Hypofractionated and Conventional Radiation Therapy: A 3-Year Follow-Up

Toassess the effect of radiation therapy on lung function over the course of 3years. Evolution of restrictive and obstructive lung function parameters was investigated in 108 breast cancer participants in a randomized, controlled trial comparing conventional radiation therapy (CR) and hypofractionated tomotherapy (TT) (age at inclusion ranging 32-81years). Spirometry, plethysmography, and hemoglobin-corrected diffusing capacity were assessed at baseline and after 3months and 1, 2, and 3years. Natural aging was accounted for by considering all lung function parameters in terms of percent predicted values using the most recent reference values for women aged up to 80years. In the patients with negligible history of respiratory disease or smoking (n=77), the greatest rate of functional decline was observed during the initial 3months, this acute decrease being more marked in the CR versus the TT arm. During the remainder of the 3-year follow-up period, values (in terms of percent predicted) were maintained (diffusing capacity) or continued to decline at a slower rate (forced vital capacity). However, the average decline of the restrictive lung function parameters over a 3-year period did not exceed 9% predicted in either the TT or the CR arm. Obstructive lung function parameters remained unaffected throughout. Including also the 31 patients with a history of respiratory disease or more than 10 pack-years showed a very similar restrictive pattern. In women with breast cancer, both conventional radiation therapy and hypofractionated tomotherapy induce small but consistent restrictive lung patterns over the course of a 3-year period, irrespective of baseline respiratory status or smoking history. The fastest rate of lung function decline generally occurred in the first 3months.

Lower Airway Obstruction Is Associated with Increased Vaso-Occlusive Pain Episodes in Adults with Sickle Cell Anemia

Background: Vaso-occlusive pain episodes (VOE) are the most common complication and reason for hospital admission in individuals with Sickle Cell Anemia (SCA). Recently our team demonstrated that in adults with SCA followed prospectively for approximately 5 years, a lower baseline Forced Expiratory Volume in 1 second percent predicted (FEV1%), which is associated with earlier mortality, but evidence of obstructive or restrictive lung function patterns is not (Blood 2015, in press). Based on the evidence that abnormal pulmonary function is associated with earlier mortality, we tested the hypothesis that baseline pulmonary function patterns were associated with SCA-related morbidity, including VOE and acute chest syndrome (ACS) events.Procedure: A prospective cohort of adults with SCA followed in the Cooperative Study for Sickle Cell Disease (CSSCD) was constructed based on a planned secondary analysis. Data from the first PFT record at age 21 and older were used for this study. Percent predicted values were determined for each participant based on their age, gender, height, and race for FEV1 and the ratio of FEV1 to forced vital capacity (FEV1/FVC) using the Global Lung Function 2012 equations (Eur Respir J, 2012; 40(6): 1324-1343). Assessment of lower airway obstruction was based on % predicted FEV1/FVC. Percent predicted total lung capacity (TLC), a measure of restrictive lung disease, was determined using published equations and corrected based on race. All PFT evaluations were checked for quality. Negative binomial regression models were used to determine the association between future VOE, ACS events, and spirometry measurements after adjusting for age, sex, hemoglobin, and fetal hemoglobin levels.Results: A total of 430 adults with SCA were evaluated. Ages of the study participants ranged from 21.7-66.4 years with a median age of 32.6 years at the time of first PFT and median follow-up was 5.5 years. Only FEV1/FVC% predicted as a continuous covariate was a significant predictor of future VOE. Lower FEV1/FVC% predicted was associated with higher future pain event rates with a rate ratio of 1.022 (95% CI 1.002 - 1.042; p=0.028). For every 10% decrease in FEV1/FVC% predicted there is a 23% increase in the rate ratio. TLC% predicted did not predict future VOE (p=0.762). FEV1/FVC% predicted or TLC% predicted did not predict future ACS events (p=0.618 and p=0.430 respectively). When FEV1/FVC% predicted and TLC% predicted < 5th percentile were used in the regression equation instead of continuous values, neither abnormal lung function parameter was associated with an increased incidence of VOE or ACS events.Conclusions: For the first time, we have demonstrated that spirometry evaluation with FEV1/FVC% predicted, as a measure of lower airway obstruction, identifies a group of adults with SCA at increased risk for future vaso-occlusive pain episode.Table 1CovariateRate Ratio (95% CI)PAge at PFT*-.112 (.850, .941).000Male1.032 (.581, 1.836).914Average Fetal Hemoglobin.985 (.894, 1.085).754Average Hemoglobin.954 (.763, 1.193).682Negative FEV1/FVC percent predicted**.022 (1.002, 1.042).028Final Negative Binomial Regression model for vaso-occlusive pain episodes after lung function testing (N= 430)*PFT is Pulmonary Function Test** Negative FEV1/FVC percent is reverse-coded so that lower values are associated with rate ratios above 1. DisclosuresNo relevant conflicts of interest to declare.

Abstract 13333: Restrictive Lung Function is Related to Sympathetic Hyperactivity in Patients With Chronic Heart Failure

Introduction: Sympathoexcitation and impaired lung function are common characteristics of patients with severe heart failure (HF). However, whether impaired lung function is associated with sympathoexcitation independently of HF severity remains unknown. Hypothesis: We postulated that impaired lung function itself is associated with sympathetic overactivation independently of HF severity. Methods: Muscle sympathetic nerve activity and clinical variables were determined in 83 HF patients with left ventricular ejection fraction (LVEF) &lt; 0.45. Abnormal spirometric findings with restrictive and obstructive changes were defined as reduced forced vital capacity (%FVC) &lt; 80% and a ratio of forced expiratory volume in the first second to FVC (FEV1.0%) &lt; 70%, respectively. Results: Restrictive and obstructive changes were identified in 17 and 21 patients, respectively. Muscle sympathetic nerve activity was higher in patients with, than without restrictive changes (p&lt;0.01), but comparable in those with or without obstructive changes. Univariate analyses showed that %FVC, glomerular filtration rate, specific activity scale, brain natriuretic peptide level, LVEF, age and use of aldosterone receptor blockers were significant predictors of burst incidence. Multivariate analysis revealed that %FVC, LVEF and glomerular filtration rate were common independent factors of increased burst rate and burst incidence. Changes in %FVC during follow-up negatively correlated with changes in burst rate (n=11, p&lt;0.01). Conclusions: Restrictive lung function is associated with increased sympathetic nerve activity independently of HF severity.