Abnormal Pulmonary Function Tests Research Articles

Assessment of pulmonary outcomes, exercise capacity, and longitudinal changes in lung function in pediatric survivors of high-risk neuroblastoma.

Survivors of high-risk neuroblastoma (NB) are exposed to multimodality therapies early in life and confront late therapy-related toxicities. This study assessed respiratory symptoms, exercise capacity, and longitudinal changes in pulmonary function tests (PFTs) among survivors. Survivors of high-risk NB followed in the long-term follow-up clinic at Memorial Sloan Kettering Cancer Center were enrolled. Symptom and physical activity questionnaires were completed. Medical records were reviewed for treatments and comorbidities. Participants completed spirometry, plethysmography, diffusion capacity of the lung for carbon monoxide, 6-minute walk tests (6MWTs), and cardiopulmonary exercise testing. Questionnaires and PFTs were repeated at least one year after enrollment. Sixty-two survivors participated (median age at study: 10.92 years; median age at diagnosis: 2.75 years; median time since completion of therapy: 5.29 years). Thirty-two percent had chronic respiratory symptoms. Seventy-seven percent had PFT abnormalities, mostly mild to moderate severity. Thirty-three completed 6MWTs (median, 634.3 meters); eight completed cardiopulmonary exercise tests (mean VO2 max: 63% predicted); 23 completed a second PFT revealing declines over a median 2.97 years (mean percent predicted forced vital capacity: 79.9 to 70.0; mean forced expiratory volume in 1 second: 81.6 to 69.9). Risks for abnormalities included thoracic surgery, chest radiation therapy (RT), thoracic surgery plus chest RT, and hematopoietic stem cell transplant. In this cohort of survivors of high-risk NB, PFT abnormalities were common but mostly mild or moderate. Maximal exercise capacity may be affected by respiratory limitations and declines in lung function may occur over time. Continued pulmonary surveillance of this at-risk population is warranted.

Respiratory Complications in Patients with Hyper IgM Syndrome

Hyper Immunoglobulin M (HIgM) syndrome is a heterogeneous group of primary immunodeficiency disorders, characterized by recurrent infections and associated with decreased serum IgG and IgA, but normal or increased IgM. The aim of the present study was to evaluate respiratory manifestations in patients with HIgM syndrome. A total number of 62 patients, including 46 males and 16 females were included in the present study. To investigate the respiratory complications among HIgM patients, we evaluated the clinical hospital records, immunologic and molecular diagnostic assays, pulmonary function tests (PFT), and high-resolution computed tomography (HRCT) scans. Pneumonia was the most common respiratory manifestation (n = 35, 56.4%), followed by otitis media (45.1%), sinusitis (33.8%), and bronchiectasis (14.5%). 52.1% of the patients had abnormal PFT results, with a predominant restrictive pattern of changes. HRCT scans demonstrated abnormal findings in 85.7% of patients with found mutations. Ten cases had hilar lymphadenopathy and para-hilar infiltrates in their HRCT findings. Genetic diagnosis was confirmed in 29 HIgM patients (72.4% CD40 ligand (CD40L) and 24.1% activation-induced cytidine deaminase (AICDA/AID) deficiencies). Majority of patients with CD40L (71.4%) and AID (57.1%) deficiencies had missense mutations. Pneumonia and abnormal high-resolution computed tomography (HRCT) findings were more frequent among patients with CD40L mutation. Respiratory failure constituted the major cause of mortality (37.5%) with majority of cases occurring in CD40L-deficient patients (50%). Respiratory complications are common in patients with HIgM syndrome. A proper awareness of respiratory manifestations in patients with HIgM may result in improved management, reduced morbidity and mortality, and an improvement in the quality of life of the patients.

Fatigue in young people with Duchenne muscular dystrophy.

To describe fatigue in Duchenne muscular dystrophy (DMD) from patients' and parents' perspectives and to explore risk factors for fatigue in children and adolescents with DMD. A multicentre, cross-sectional study design was used. Seventy-one patients (all males; median age 12y, age range 5-17y) identified via the Canadian Neuromuscular Disease Registry, and their parents completed questionnaires. Subjective fatigue was assessed using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale by child self-report and parent proxy-report. Patients with DMD across ages and disease stages experienced greater fatigue compared to typically developing controls from published data. Sleep disturbance symptoms were associated with greater fatigue by child self-report (ρ=-0.42; p=0.003) and parent proxy-report (ρ=-0.51; p<0.001). Depressive symptoms were associated with greater fatigue by child self-report (ρ=-0.46; p<0.001) and parent proxy-report (ρ=-0.45; p<0.001). Lower functional ability was associated with greater fatigue by parent proxy-report (ρ=0.26; p=0.03). Physical activity level, and musculoskeletal, respiratory, and cardiac function were not associated with fatigue. In paediatric DMD, sleep disturbance symptoms and depressive symptoms are potentially modifiable factors associated with fatigue, warranting additional investigation to facilitate the development of therapeutic strategies to reduce fatigue. Fatigue is a major issue in paediatric Duchenne muscular dystrophy (DMD) across ages and disease stages. Sleep disturbance and depressive symptoms are significantly associated with fatigue in paediatric DMD.

Asymptomatic respiratory dysfunction in patients with gastroesophageal reflux disease

BACKGROUND: Gastroesophageal reflux disease is the primary cause for many conditions affecting extraesophageal structures. OBJECTIVE: The objective of the study is to investigate the relation between reflux disease and asymptomatic respiratory dysfunction and examine correlation between the respiratory dysfunction with severity of gastroesophageal reflux disease (GERD) spectrum. METHODOLOGY: A total of 242 patients were subjected to pulmonary function test (PFT) using spirometer-G procedures. Forced expiratory volume 1 s (FEV1), forced vital capacity (FVC), FEV1/FV C ratio, and peak expiratory flow rate (PEFR) were measured. Patients in test group were treated with proton-pump inhibitor (PPI) and esomeprazole 40 mg twice daily for 3 months. They were subjected to PEFR at the end of the study. Analysis was performed using SPSS version. RESULTS: Age and PFT parameters FEV1, forced expiratory flow (FEF) 25–75, PEF, and PEFR were compared groupwise and were found to be statistically significant except FEV. As the severity of GERD increases, severity of pulmonary disorder also increases. In Group 1A, 56.5% patients had normal PEFR and 43.4% PEFR was reduced showing statistically significant. In patients with abnormal PFT, 74.2% had mild esophagitis, 15.1% had moderate esophagitis, and 10.6% had severe esophagitis showing statistically significant. Mean PEFR before treatment showed 344.1 ± 79.22. After 3 months of esomeprazole 40 mg, twice daily mean increased 409.08 ± 100.00. In Group 1B, PEFR before treatment noted 342.0 ± 53.77. Significant improvement was seen in PEFR with mean of 506.00 ± 52.64 with PPIs. CONCLUSIONS: GERD is associated with asymptomatic respiratory dysfunction. There is strong and direct relationship between the severity of respiratory disorders, detected by FEV1 and FEV1/FVC, FEF25–75, PEF, PEFR, and severity of GERD. This study demonstrated significant improvement in PEFR values, with adequate treatment of GERD.

Identifying Alpha-1 Antitrypsin Deficiency Based on Computed Tomography Evidence of Emphysema.

IntroductionChronic obstructive pulmonary disease (COPD) is most commonly caused by smoking tobacco or cigarettes. However, alpha-1 antitrypsin deficiency (AATD) is the only genetic disorder known to cause COPD and these patients often present with emphysema earlier in life and with more severe disease. Additionally, AATD patients are often misdiagnosed with other lung disorders, and the diagnosis is often delayed for up to a decade. Furthermore, several clinicians may see the patient before genetic testing is performed and an official diagnosis is made. We hypothesized that patients with radiographic emphysema on computed tomography (CT) scan of the chest would represent an enriched population of patients with a higher prevalence of alpha-1 antitrypsin (AAT) carrier or heterozygous state.MethodsWe evaluated 250 in-patients with chest computed tomography (CT) findings of emphysema, and per clinical guidelines, all were tested for AAT with Alphakit finger stick blood collection kits. Sampling 250 patients provided power to detect a carrier prevalence of 20% +/- 1.0%.ResultsA total of 250 patients were recruited of which 53% were male, 91% Caucasian, 7% African American, and 16% active smokers. They smoked an average of 39 packs per year. The prevalence of carrier status (Pi*MS or Pi*MZ) was 6.8% (95% CI (4%, 11%)). The mean forced expiratory volume in one second (FEV-1) was 53%, predicted among Pi*MM patients (n=126) and not significantly different from the Pi*MS group (50%, n=13). 69% of Pi*MM were diagnosed with asthma or COPD, vs. 79% of Pi*MS (n=14) and 100% Pi*MZ (n=3), but the difference was not significant (p=0.4).ConclusionIn the population studied, compared to a cohort of patients with abnormal pulmonary function tests (PFTs), radiographically evident emphysema did not identify patients at higher risk of being heterozygous or homozygous for AAT deficiency.

Impact of biomass fuel exposure from traditional stoves on lung functions in adult women of a rural Indian village

Introduction:Exposure to biomass fuel (BMF) from traditional cookstoves inflicts an enormous burden of morbidities in women across the developing world. This study aims to assess the lung function and its association with the indoor air pollutants generated using BMF.Materials and Methods:This cross-sectional study including 310 women was conducted in a rural village of India. Households were divided into two groups based on the cooking fuel, the BMF group and the liquefied petroleum gas (LPG) group. Information on respiratory symptoms and socioeconomic status was obtained using a standard questionnaire. Indoor air concentration for PM10 and PM2.5 was measured during cooking hours. Pulmonary function tests (PFTs) were conducted for the women inhabitants.Results:On comparing the two groups, the concentration of PM10 (890.26 ± 59.59 vs. 148.66 ± 31.97) μg/m3 and PM2.5 (728.90 ± 50.20 vs. 99.76 ± 41.80) μg/m3 (P < 0.01) were higher in the group using BMF. The respiratory symptoms such as wheezing, dyspnea, chronic cough, and nocturnal cough, were significantly more common in the group using BMF. A significant difference was seen in the lung function indices between the two groups. A significant negative correlation of respiratory indices with duration of exposure and the particulate matter (PM) values suggested a greater decline on lung function among women exposed to increased concentrations of PM. On comparing participants with normal and abnormal PFT, it was seen that the use of BMF (odds ratio [OR] 8.01; 95% confidence interval [CI] 4.80, 13.36, P < 0.001) and the duration of exposure to BMF (OR 1.16; 95% CI 1.13, 1.20., P < 0.001) increased the odds of having an abnormal PFT.Conclusions:This study shows a high prevalence of respiratory symptoms and an abnormal pulmonary function in women exposed to BMF.

Abnormal Nailfold Capillaroscopy Is Common in Patients with Connective Tissue Disease and Associated with Abnormal Pulmonary Function Tests.

To assess the presence of a systemic sclerosis (SSc) pattern on nailfold capillary microscopy (NCM) in patients with Raynaud phenomenon (RP) and to explore its association with abnormal pulmonary function tests (PFT). NCM patterns were assessed in 759 consecutive patients with RP. Patterns were classified as normal (n = 354), nonspecific (n = 159), or SSc pattern (n = 246). Abnormal PFT was defined as forced vital or diffusion capacity < 70%. Patients were classified as primary RP (n = 245), or secondary: no definite diagnosis (n = 391), SSc (n = 40), primary Sjögren syndrome (pSS; n = 30), systemic lupus erythematosus (SLE; n = 30), mixed connective tissue disease (MCTD; n = 7), rheumatoid arthritis (RA; n = 15). An SSc pattern on NCM was frequently observed in most patients with a definite diagnosis: SSc (88%), pSS (33%), SLE (17%), MCTD (71%), and RA (13%). In patients without definite diagnosis, 17% had a normal NCM pattern, 35% nonspecific, and 48% SSc pattern. Abnormal PFT was more frequent in patients with an SSc pattern (35.9% vs 19.5%, p = 0.002), even when corrected for SSc diagnosis (p = 0.003). Absence of an SSc pattern had high negative predictive value (88%); positive predictive values were low. SSc pattern on NCM is common in patients with RP, and in those with connective tissue diseases other than SSc. It is associated with a higher prevalence of abnormal PFT, independent of the presence of an SSc diagnosis. Although these data need validation in a prospective setting, they underline the importance of NCM in RP and putative value to stratify the risk of pulmonary involvement in early stages of disease.

Pulmonary Function Abnormalities in Adults with Sickle Cell Anemia

Sickle cell anemia (SCA) is an inherited red blood cell disorder that leads to hemoglobin polymerization when it deoxygenates. Lung function abnormalities are observed in up to 90% of adults with SCA (PMID: 16556694) and both the prevalence (PMID: 20644948) and rate of FEV1 decline (PMID: 18383325) are greater in SCA adults compared to the general population. Furthermore, low FEV1 is an independent predictor of early mortality in SCA (PMID: 26261241). Understanding the risk factors and mechanisms for abnormal lung function, which can impact blood oxygen and pH levels, is especially important in SCA.We evaluated the clinical, laboratory, and genetic risk factors for abnormal pulmonary function in a retrospective cohort of SCA patients. Pulmonary function test (PFT) abnormalities were categorized based on the American Thoracic Society/European Respiratory Society Guidelines. Alpha-thalassemia and BCL11A rs1427407 status were determined by PCR. Continuous and categorical variables were compared using the Kruskal-Wallis and Chi-square test, respectively, and Kaplan-Meier curves and Cox proportional hazards models were used to compare survival patterns. Median and interquartile ranges (IQR) are provided.Between 12/2004 and 12/2015, 90 SCA adult patients had PFTs performed as part of their routine medical care. The median age of the cohort was 37 years (IQR, 24-47years), 46% were male, 59% were on hydroxyurea, and 28% were cigarette smokers. Abnormal pulmonary function was observed in 56 (62%); 32 (35.6%) had obstructive, 15 (16.7%) had restrictive, and 9 (10%) had mixed lung defects. SCA patients with abnormal PFTs were more anemic (8.4 vs. 9.0g/dL, P=0.004), had higher LDH (441 vs. 306U/L, P=0.002) and urine albumin concentrations (180 vs. 29mg/g creatinine, P=0.004), and a lower hemoglobin F% (4.2% vs. 8.0%, P=0.004) compared to SCA with normal PFTs. SCA patients who inherited the BCL11A rs1427407 T allele had a lower prevalence of abnormal PFTs (G/G: 67%, G/T: 55%, T/T: 50%; P=0.2), but this was not statistically significant, and we did not observe any patterns between co-inheritance of α-thalassemia and abnormal PFTs (αα/αα: 60%, α-/αα: 64%, α-/α-: 60%; P=0.9). On logistic regression analysis, LDH (natural log OR 8.2, P=0.03) was independently associated with abnormal pulmonary function after adjusting for age, gender, and hydroxyurea use. SCA patients with abnormal pulmonary function had earlier mortality compared to those with normal pulmonary function (Figure 1) (log-rank P=0.03; age-adjusted HR 6.1, P=0.09).Next, we analyzed clinical and laboratory risk factors associated with obstructive or restrictive lung disease. Lower hemoglobin F% and a greater prevalence of tricuspid regurgitant velocity (TRJV) > 3.0m/s were associated with both restrictive and obstructive pulmonary function compared to normal pulmonary function (Table 1). In addition, lower hemoglobin concentration and higher LDH were associated with restrictive lung disease while less common treatment with hydroxyurea and higher urine albumin concentration were associated with obstructive lung disease compared to SCA patients with normal PFTs (Table 1). SCA patients with restrictive lung disease had a lower oxygen saturation, determined by pulse oximetry, compared to those with normal PFTs (P=0.02) while no difference in oxygen saturation was observed between those with obstructive versus normal PFTs (P=0.6) (Figure 2). Mortality risk was significantly increased for SCA patients with restrictive (age-adjusted HR 2.0, P=0.01) but not obstructive lung disease (age-adjusted HR 1.6, P=0.4) compared to those with normal PFTs (log rank P=0.006) (Figure 3).In conclusion, we demonstrate that increased hemolysis is associated with abnormal pulmonary function based on a lower hemoglobin concentration and lower hemoglobin F% and higher LDH. We also demonstrate that restrictive-type lung disease is associated with a lower oxygen saturation and increased mortality risk compared to those with normal PFTs. Future studies investigating the role of hemolysis in lung disease and therapies to improve pulmonary function, particularly in those with restrictive lung disease, are warranted in SCA. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pulmonary effects on exercise testing in tetralogy of Fallot patients repaired with a transannular patch.

A transannular patch is often used in the contemporary surgical repair of tetralogy of Fallot. This can lead to significant pulmonary insufficiency and increased right ventricular volumes and ultimately pulmonary valve replacement. Cardiopulmonary exercise testing is used to assess exercise capacity in tetralogy of Fallot patients before pulmonary valve replacement. There is only few published literatures on how lung function affects functional capacity in tetralogy of Fallot patients repaired with a transannular patch. A retrospective chart review was done from 2015 to 2017 on patients with tetralogy of Fallot who underwent maximal effort cardiopulmonary exercise testing with cycle ergometry and with concurrent pulmonary function testing. Tetralogy of Fallot patients repaired with a transannular patch without pulmonary valve replacement were compared with age, gender, and size-matched normal controls. In the tetralogy of Fallot group, 24 out of 57 patients underwent primary repair with a transannular patch. When compared to the normal controls, they demonstrated abnormal predicted forced expiratory volume in one second (79 ± 23.1% versus 90.7 ± 14.1%, p&lt;0.05), predicted maximal voluntary ventilation (74 ± 18% versus 90.5 ± 16.2%, p&lt;0.05) while having low-normal predicted forced vital capacity (80.5 ± 17.2% versus 90.2 ± 12.4%, p&lt;0.05) and normal breathing reserve percentage (50.3 ± 11.3% versus 47.5 ± 17.3%, p = 0.52). Cardiopulmonary exercise testing abnormalities included significantly lower percent predicted oxygen consumption (63.2 ± 12.2% versus 87 ± 12.1%, p&lt;0.05), maximal heart rate (171.8 ± 18.9 versus 184.6 ± 13.6, p&lt;0.05), and percent predicted maximum workload (61.7 ± 15.9% versus 88.3 ± 21.5%, p&lt;0.05). Tetralogy of Fallot patients repaired with a transannular patch can have abnormal pulmonary function testing with poor exercise capacity in addition to chronotropic incompetence and impaired muscular power.

Are We Choosing Wisely With Autologous Hematopoietic Cell Transplantation Screening? The Utility of Pulmonary Function Testing Prior to Autologous Hematopoietic Cell Transplantation

IntroductionDespite the risk of morbidity and mortality associated with autologous hematopoietic cell transplantation (ASCT), there are no clear guidelines as to how to screen for these risks. This study sought to determine the utility of pulmonary function tests (PFTs) prior to ASCT on predicting posttransplant clinical outcomes. Patients and MethodsPatients undergoing ASCT between 2010 and 2012 at the Ottawa Hospital (n = 172) were reviewed. PFT results prior to ASCT were retrieved. The primary outcomes were incidence of intensive care unit (ICU) admission, Seattle Criteria for pulmonary toxicities, and transplant-related mortality (TRM). ResultsPFTs were performed for 91 (53%) patients prior to ASCT. There were more smokers in the PFT cohort than the non-PFT cohort (41.8% vs. 19.8%, respectively; P < .0001). Pulmonary toxicity as measured by the Seattle Criteria did not correlate with PFT results (normal vs. abnormal, 8.1% and 6.1%, respectively; P = 1.00). There were no differences in incidence of ICU admission by PFT result (normal vs. abnormal, 2.7% vs. 8.2%, respectively; P = .61) and no difference in TRM by PFT result (normal vs. abnormal, 0% vs. 2.0%, respectively; P = 1.00). ConclusionDespite testing patients deemed higher risk for pulmonary toxicity, abnormal PFTs did not predict for an increased risk of pulmonary toxicity, ICU admission, or TRM at our center.

Pulmonary Acute and Late Effects after Radiation for Childhood Cancer: A Report From the PENTEC (Pediatric Normal Tissue Effects in the Clinic) Initiative

The PENTEC pulmonary task force aims to quantify radiation dose-volume effects among children treated for cancer, taking into account impact of multimodality therapy (radiation therapy [RT], chemotherapy, and surgery). This report focuses on acute and late radiation pneumonitis (RP), lung fibrosis, abnormal pulmonary function tests (PFTs), supplemental oxygen need, dyspnea, chronic cough and impaired exercise tolerance. A comprehensive search of PubMed databases from 1965-2017 was conducted using key words related to acute and late effects of pulmonary radiation in cancer patients < 21y. The identified papers were reviewed to develop a predictive model of lung injury following radiation in this vulnerable population. RP grade was based on Common Terminology Criteria for Adverse Events (CTCAE) and Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) criteria, and other clinical outcomes were reported using CTCAE and questionnaires. For RP analysis, lung dose was calculated from dose-volume histogram (DVH) data. The search identified > 2,300 publications, from which 432 papers with detailed treatment and toxicity data were selected for further review. DVH data was extracted from 9 papers for modeling. The cohorts analyzed for acute and late RP included 139 and 254 patients, respectively, aged 0.04-22.7y, treated from 2000-2013. Clinical outcomes data included 14,985 patients, aged 0-21.9y, treated from 1970-2009. RP in pediatric patients receiving RT to all or part of the thorax was minimal, with 4% acute (range, 0-4%) and 4% late (range, 1.6-17.4%) grade 2 RP from the pooled analysis. No higher grade RP was reported. Abnormal PFTs correlated with dose, but patients were often asymptomatic; however, cooperation with pulmonary function and exercise testing was challenging in the pediatric cohort. Large multi-institutional studies showed relationship between doses > 10 Gy and abnormal PFTs, clinical outcomes (dyspnea, chronic cough, supplemental oxygen need, lung fibrosis, recurrent pneumonia), and pulmonary deaths at ≥ 10-y follow-up. Multivariate analyses (MVA) in two studies demonstrated that bleomycin does not contribute to adverse pulmonary outcomes at doses used in contemporary treatment regimens (n=510, RR: 1.2, CI: 0.8-1.8 and n=64, p=0.14, respectively). Extent of thoracic surgery showed variable impact on lung function in this cohort. Pediatric RT to the thorax results in low frequency and severity of both acute and late pulmonary toxicity. Unlike lung toxicity studies for adults, single-institution pediatric cohorts are often small, making MVA difficult. Larger multi-institutional trials and registries with DVH data and long-term follow-up are needed to determine correlations between RT and acute and late lung toxicity in children treated for cancer.

Pulmonary Complications of Total Body Irradiation in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation: Results from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) Initiative

Pulmonary toxicity is a potential complication of total body irradiation (TBI) delivered as part of hematopoietic cell transplantation (HCT) conditioning. The PENTEC stem cell task force aims to systematically determine the incidence and severity of TBI-associated acute and chronic lung injury and to quantify TBI related risk factors among pediatric HCT patients. A systematic literature search was conducted using Medline, PubMed, and Cochrane library databases from 1980 through 2016 for all articles describing pulmonary toxicity in children treated with HCT. Only English language reports where patients were either all ≤21 years old, or had a median age ≤21 years with patients stratified by age were included. Data pertaining to TBI and pulmonary endpoints were extracted. Risk of acute and chronic lung injury was analyzed in relation to patient age, TBI dose, fractionation, lung shielding, timing, and type of transplant. Of 3,049 identified studies, 3,025 were excluded due to inappropriate age and lack of details related to TBI or pulmonary toxicity. The endpoint of acute, non-infectious idiopathic pneumonitis (IP) was reported in 17 papers with incidences ranging from 0-33% (median 11%). Mortality, when reported, was high (median 78%, range 37.5-100%). IP rates among reports with median patient ages <10 years was not significantly different than in reports with median ages >10 (8.5% vs. 12.5%). Total TBI doses ranged from 7.5 to 17 Gy given in 1.2-10 Gy per fraction at dose rates between 5 and 26 cGy/minute. TBI factors associated with a higher rate of IP were difficult to discern as variables were often reported in combination. Dose rate of <15 cGy minute was associated with a lower incidence of IP in a single report. The effect of lung shielding was inconclusive as was the protective effect of fractionation. Long-term pulmonary function abnormalities were present in 40-100% of patients based on 7 evaluable studies, but usually of a mild or moderate degree. Restrictive abnormalities were more frequent than obstructive disorders and many patients were asymptomatic despite a decline in pulmonary function testing (PFT). Pulmonary toxicity is a potentially serious complication following TBI in the setting of HCT. Based on a limited number of evaluable studies, the rates of IP were low among pediatric patients. While PFT abnormalities were common, few patients became symptomatic. Lower dose rate of TBI may be protective of IP, but the effects of other practices, such as lung blocking and fractionation are unclear.

PULMONARY FUNCTION TEST PARAMETERS IN DIFFUSE AND LIMITED SCLERODERMA

SESSION TITLE: Pulmonary Manifestations of Systemic Disease SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: Scleroderma is characterized by varying degrees of organ fibrosis and obliterative vasculopathy. Lung involvement is the leading cause of morbidity in Scleroderma. The spectrum of Pulmonary Function Test (PFT) abnormalities in Scleroderma has been reported to be variable, with a recent study revealing that PFTs have a low sensitivity in detecting Scleroderma-related interstitial lung disease, with false negative cases more common in diffuse Scleroderma. The objectives of this study are to determine the spectrum of PFT abnormalities in Scleroderma and to compare PFTs in limited and diffuse Scleroderma. METHODS: We reviewed the records of 174 Scleroderma patients followed at the rheumatology clinic in our institution. Patient demographics and PFT parameters [FEV1, FVC, FEV1/FVC, TLC and DLCO percent predicted (%)] were noted in patients with limited (Scl-Ltd) and diffuse (Scl-Diffuse) disease. Obstruction was defined as FEV1/FVC < 70%; restriction as TLC < 80% and impaired diffusion as DLCO < 80%. Severity of restriction was defined per ATS criteria. PFT parameters in the two groups were compared by Student’s t-test. p < 0.05 was deemed statistically significant. RESULTS: Mean age: 65 +/- 12.2 years; 91% were females; 76.4% had Scl-Ltd. Mean FEV1 was: 92 +/- 22%; mean FVC: 88.5 +/- 21.3%; mean TLC: 91.5 +/- 18%; mean DLCO:70.5 +/- 23%. Twenty-eight % patients had normal PFTs; 12 % had obstruction, 32% had restriction and 28% patients had isolated reduction in DLCO. Thirty-five % patients with Scl-Ltd and 24.4% patients with Scl-Diffuse had a normal DLCO. In patients with restriction, 40% had mild, 51% moderate and 9% had severe restriction. PFT abnormalities were seen in 37.6% Scl-Ltd, and 56% Scl-Diffuse. PFT parameters in the 2 groups are shown below. PFT parameters in 2 groups (Table) CONCLUSIONS: Majority of Scleroderma-patients have abnormal PFTs. Restriction and impairment in diffusion were the most common abnormalities. Over 1/3rd patients with limited disease had PFT abnormalities. CLINICAL IMPLICATIONS: Whether restriction defined by TLC corelates with fibrosis on imaging need to be studied. DISCLOSURES: No relevant relationships by Debapriya Datta, source=Web Response No relevant relationships by Carol Halasan, source=Web Response No relevant relationships by Sophie Korzan, source=Web Response

Pulmonary Function Tests Abnormalities in Children With Inflammatory Bowel Disease: Is It Common?

The aim of the study was to evaluate the frequency and type of pulmonary dysfunction in newly diagnosed children with inflammatory bowel disease (IBD) and the correlation between pulmonary function tests (PFTs) and IBD activity. It is an observational case-control study. One hundred newly diagnosed children with IBD were enrolled as the patient group, which was further subdivided into 52 with Crohn disease (CD) and 48 with ulcerative colitis (UC). Fifty healthy children matched for age, sex, height, and body mass index (BMI) served as the control group. PFTs in the form of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, residual volume (RV), total lung capacity (TLC), mid-forced expiratory flow of 25% to 75% (FEF 25%-75%) and diffusing capacity of the lung for carbon monoxide (DLCO) were evaluated in all studied children. PFTs were measured at diagnosis, every 6 months for a period of 3 years, during remission and at least once during activity in patient group. There was significant progressive deterioration in all PFTs in IBD patients compared with their PFTs at the start of the study (P < 0.05) except for FEV1/FVC, RV, and TLC (P > 0.05). There was significant deterioration during disease activity compared with remission state as regards FEV1, FVC, FEF 25% to 75%, and DLCO (P < 0.05). Significant negative correlation was found between disease activity in both UC and CD groups and FEV1, FVC, FEF 25% to 75%, and DLCO. Subclinical PFTs abnormalities are common in pediatric IBD even during remission period. So, periodic PFTs evaluation should be considered in the routine follow-up of IBD children.

Study of Pulmonary function tests in Type 2 Diabetes Mellitus and their correlation with glycemic control and systemic inflammation.

Background - Reduced lung function in diabetes has been described for long but its clinical importance is not yet clear. Also, limited literature is available regarding its association with sugar control, and its correlation with inflammatory markers. Thus, we aimed to study the pulmonary function test abnormalities and systemic inflammation in type 2 diabetes mellitus. Methods 100 patients of type 2 diabetes were divided into two groups depending on control of diabetes (group A-HbA1C≤7% and group B-HbA1C >7%). All the subjects selected underwent detailed evaluation including testing for HbA1C, HsCRP (high-sensitivity C-reactive protein), serum ferritin and serum fibrinogen, along with pulmonary function testing. Results Percentage predicted FVC (forced vital capacity), FEV1 (forced expiratory volume in 1 second) and SVC (slow vital capacity) were significantly reduced, while mean values of inflammatory markers [fibrinogen (p <0.001) and hsCRP (p 0.002)] were significantly higher in uncontrolled diabetes group. There was a significant negative correlation between FEV1 (r = -0.739, p<0.001), FVC ( r = -0.370, p<0.001), SVC (r = -0.635, p< 0.001) with HbA1C. HbA1C had a positive correlation with hsCRP (r = -0.308, p 0.002) and fibrinogen (r = 0.388 ,p 0.001). Conclusion Pulmonary functions were decreased and inflammatory markers like hsCRP, fibrinogen, and ferritin significantly increased in uncontrolled diabetics. Also, a potential association was seen between higher values of inflammatory markers like hsCRP and fibrinogen and decrease in lung function. This information, requiring confirmation with larger multicentre studies, remains important because of potential epidemiological, clinical and therapeutic implications.

Pulmonary Manifestations and Progression of Lung Disease in Juvenile-onset Mixed Connective Tissue Disease.

To assess the occurrence and extent of interstitial lung disease (ILD) in patients with juvenile mixed connective tissue disease (JMCTD), compare pulmonary function in patients and matched controls, study associations between ILD and disease-related variables, and examine progression of pulmonary manifestations over time. A cohort of 52 patients with JMCTD were examined in a cross-sectional study after a mean 16.2 (SD 10.3) years of disease duration with high-resolution computed tomography (HRCT) and pulmonary function tests (PFT) comprising spirometry, DLCO, and total lung capacity (TLC). Matched controls were examined with PFT. Previous HRCT and PFT were available in 37 and 38 patients (mean 8.8 and 10.3 yrs before study inclusion), respectively. Compared to controls, patients with JMCTD had lower forced vital capacity (FVC), DLCO, and TLC (p < 0.01). The most frequent abnormal PFT was DLCO in 67% of patients versus 17% of controls (p < 0.001). Fourteen patients (27%) had ILD on HRCT. Most had ILD in < 10% of their lungs. ILD was associated with low values for FVC and TLC, but not with DLCO. HRCT findings did not progress significantly over time, but FVC declined (p < 0.01). Compared to controls, patients with JMCTD had impaired pulmonary function. ILD was present in 27% of patients after a mean 16 years of disease duration, mostly as mild disease, and did not progress. ILD seems to be less common in juvenile-onset than in adult-onset MCTD, and ILD in JMCTD seems mostly mild and stable over time.

Club cell protein 16 (Cc16) deficiency increases inflamm-aging in the lungs of mice.

Low serum CC16 levels are associated with accelerated lung function decline in human population studies, but it is not known whether low serum CC16 levels contribute to lung function decline, or are an epiphenomenon. We tested the hypothesis that unchallenged Cc16 −/− mice develop accelerated rates of pulmonary function test abnormalities and pulmonary pathologies over time compared with unchallenged WT mice. Respiratory mechanics, airspace enlargement, and small airway fibrosis were measured in unchallenged wild‐type (WT) versus Cc16 −/− mice over 6–18 months of age. Lung leukocyte counts and lung levels of metalloproteinases (Mmps), cytokines, oxidative stress, cellular senescence markers (p19 and p21), and lung cell apoptosis, and serum C‐reactive protein (CRP) levels were measured in age‐matched WT versus Cc16 −/− mice. Unchallenged Cc16 −/− mice developed greater increases in lung compliance, airspace enlargement, and small airway fibrosis than age‐matched WT mice over 6–18 months of age. Cc16 −/− mice had greater: (1) lung leukocyte counts; (2) lung levels of Ccl2, Ccl‐5, interleukin‐10, Mmp‐2, and Mmp‐9; (3) pulmonary oxidative stress levels, (4) alveolar septal cell apoptosis and staining for p16 and p21; and (5) serum CRP levels. Unchallenged Cc16 −/− mice had greater nuclear factor‐κB (NF‐κB) activation in their lungs than age‐matched WT mice, but similar lung levels of secretory phospholipase‐A2 activity. Cc16 deficiency in mice leads spontaneously to an accelerated lung aging phenotype with exaggerated pulmonary inflammation and COPD‐like lung pathologies associated with increased activation of NF‐ κB in the lung. CC16 augmentation strategies may reduce lung aging in CC16‐deficient individuals.

Impact of Lung Function on Bronchiolitis Obliterans Syndrome and Outcome after Allogeneic Hematopoietic Cell Transplantation with Reduced-Intensity Conditioning

Lung function deterioration contributes to treatment-related morbidity and mortality in patients after allogeneic hematopoietic cell transplantation (allo-HCT). Better understanding of impaired lung function including bronchiolitis obliterans syndrome (BOS) as chronic manifestation of graft-versus-host disease (GVHD) might improve outcomes of patients after allo-HCT.To detect early pulmonary function test abnormalities associated with BOS incidence and outcome after allo-HCT, we performed a retrospective analysis of homogenous-treated 445 patients (median age, 61.9 years; range, 19 to 76 years) with a reduced intensity/toxicity conditioning protocol. The cumulative incidence of BOS was 4.1% (95% confidence interval [CI], 2.6 to 6.4) at 1 year and 8.6% (95% CI, 6.3 to 11.6) at 5 years after allo-HCT with a median follow-up of 43.2 months (range, 3.3 to 209 months). In multivariate analysis, pre-existence of moderate small airway disease reflected by decreased midexpiratory flows before allo-HCT was associated with increased risk for BOS development. In addition, severe small airway disease before allo-HCT and combined restrictive/obstructive lung disease at day +100 after allo-HCT were associated with higher risk for nonrelapse mortality (NRM) due mainly to pulmonary cause of death.In summary, we identified novel pulmonary function test abnormalities prior and after allo-HCT associated with BOS development and NRM. These findings might help to identify a risk population and result in personalized GVHD prophylaxis and preventive or early therapeutic interventions.

Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung Cancer

BackgroundRadiation pneumonitis (RP) is a frequent complication of concurrent chemoradiotherapy (CCRT) and is associated with severe symptoms that decrease quality of life and might result in pulmonary fibrosis or death. The aim of this study is to identify whether pulmonary function test (PFT) abnormalities may predict RP in non-small cell lung cancer (NSCLC) patients.MethodsA prospective multi-institutional study was conducted with locally advanced and oligometastatic NSCLC patients. All participants were evaluated at baseline, end of CCRT, week 6, 12, 24, and 48 post-CCRT. They completed forced spirometry with a bronchodilator, body plethysmography, impulse oscillometry, carbon monoxide diffusing capacity (DLCO), molar mass of CO2, six-minute walk test and exhaled fraction of nitric oxide (FeNO). Radiation pneumonitis was assessed with RTOG and CTCAE. The protocol was registered in www.clinicaltrials.gov (NCT01580579), registered April 19, 2012.ResultsFifty-two patients were enrolled; 37 completed one-year follow-up. RP ≥ Grade 2 was present in 11/37 (29%) for RTOG and 15/37 (40%) for CTCAE. Factors associated with RP were age over 60 years and hypofractionated dose. PFT abnormalities at baseline that correlated with the development of RP included lower forced expiratory volume in one second after bronchodilator (p = 0.02), DLCO (p = 0.02) and FeNO (p = 0.04). All PFT results decreased after CCRT and did not return to basal values at follow-up.ConclusionsFEV1, DLCO and FeNO prior to CCRT predict the development of RP in NSCLC. This study suggests that all patients under CCRT should be assessed by PFT to identify high-risk patients for close follow-up and early treatment.

Assessment of pulmonary function test abnormalities in adult survivors of childhood cancer.

117 Background: As childhood cancer survival approaches 85%, it is increasingly recognized that childhood cancer survivors (CCS) are at risk for long-term therapy-related complications. Data suggest that pulmonary function test (PFT) abnormalities occur in as many as 84.1% of CCS. Our aim was to assess the prevalence and nature of respiratory abnormalities in adult CCS and to correlate these abnormalities with therapeutic exposures and health behaviors. Methods: Patients who received pulmonary toxic therapy routinely undergo PFTs at their first visit to the POGO AfterCare clinic in Ottawa, Canada. We conducted a retrospective review of all patients seen in clinic from August 2015 until December 2016. PFT results, treatment exposures and health habits were documented. We used NHANES-III prediction equations for PFT interpretation, with expiratory flows and lung volumes of ≥80% predicted as cutoffs for normal. Results: Of a total of 200 patients, 48 received pulmonary toxic therapy and 38 underwent PFTs. Mean age at the time of PFT was 28.8 years (18.5-57.5 years) and the mean time from diagnosis was 17.4 years (3.4-47.5 years). Although no patients reported respiratory symptoms, 42% (16/38) demonstrated a mild restrictive ventilatory defect, 11% (4/38) had mild airflow obstruction, 18% (7/38) had an isolated reduction in diffusion capacity and 1 patient had a moderate mixed obstructive/restrictive abnormality. Only 26% (10/38) had normal lung function. Of those with restrictive defects, all received radiation and 50% were also exposed to pulmonary toxic chemotherapy. All patients with obstructive defects received radiation therapy in combination with bleomycin. Tobacco or marijuana use was reported in 26% (10/38) of the cohort, and in 29% (8/28) of those with PFT abnormalities. Conclusions: PFT abnormalities are common among adult CCS who received pulmonary toxic therapy. Studies evaluating the change in pulmonary function abnormalities over time and their correlation to cardiopulmonary exercise testing and lung imaging are required to inform the health impact on these survivors.