Abnormal Pulmonary Function Tests Research Articles

Effect of automobile exhaust on pulmonary function tests among traffic police personnel in Kashmir valley.

Background:Automobile exhaust is an important cause of air pollution, which is a leading health menace and is growing perpetually. Traffic police personnel are exposed to automobile exhaust more than anyone else, and the resulting lung involvement may be asymptomatic.Materials and Methods:This observational cross-sectional study was conducted among 136 traffic police personnel, aged 18–59 years, working for more than 6 months in the traffic police of Kashmir valley. In addition, 140 age- and sex-matched, healthy unexposed Kashmiri’s served as controls. Pulmonary functions were measured by RMS Helios 401 PC based spirometer.Results:Sixteen (11.2%) out of 136 traffic police personnel had abnormal pulmonary function test (PFT) as compared to 5 (3.6%) out of 140 controls. Traffic police personnel’s had significantly declined forced expiratory volume in 1 s (FEV 1) and forced vital capacity. Eight (5.8%) had obstructive, 7 (5.1%) had restrictive, and 1 (0.7%) traffic police personnel had mixed pattern on PFT. Duration of exposure to automobile exhaust of more than 10 years was significantly associated with pulmonary function abnormality (P = 0.038).Conclusion:Air pollution due to automobile exhaust may be the factor responsible for pulmonary function abnormalities in traffic police personnel. Besides protective measures during duty hours, traffic police personnel should be subjected to periodic assessment of their lung functions.

Multi‐disciplinary collaborative consensus guidance statement on the assessment and treatment of breathing discomfort and respiratory sequelae in patients with post‐acute sequelae of SARS‐CoV‐2 infection (PASC)

<scp>Multi‐disciplinary</scp> collaborative consensus guidance statement on the assessment and treatment of breathing discomfort and respiratory sequelae in patients with <scp>post‐acute</scp> sequelae of <scp>SARS‐CoV</scp>‐2 infection (<scp>PASC</scp>)

Study of Pulmonary Function Tests in Multitransfused Children with Thalassaemia: A Case-control Study

Introduction: Lung involvement is one of the known complications of thalassaemia. This study was undertaken to assess the predominant type of pulmonary dysfunction. Most studies show pulmonary function abnormalities but the results are conflicting. Aim: To study Pulmonary Function Tests (PFTs) in multitransfused children with thalassaemia and compare them with normal children. Materials and Methods: This was a case-control study conducted from May 2012 to June 2013 at MS Ramaiah Medical College, Bengaluru, Karnataka, India, which included 35 children in the age group of 3-16 years with β-thalassaemia major and on regular transfusion as cases and 35 age and sex matched healthy children participated as controls. PFTs were done in 35 children with β-thalassaemia major, using Spirobank G and within three days of blood transfusion. Following parameters were recorded: Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV1), Ratio of Forced Expiratory Volume in 1 second to Forced Vital Capacity (FEV1/FVC), Peak Expiratory Flow Rate (PEFR), and Forced Expiratory Flow (FEF25%-75). Student’s’ test was used for statistical analysis. Results: Percentage abnormalities of PFT in thalassaemia children were observed, 20 (57.14%) children had normal PFTs. Among the remaining children 9 (25.71%), 5 (14.29%) and 1 (2.86%) had restrictive, obstructive and mixed pattern of abnormalities respectively. Conclusion: Pulmonary function appeared to be affected in a majority of subjects with thalassaemia. Abnormal patterns of lung function were common in which restrictive type was predominant. No respiratory symptoms was found in any of these children. Studies are needed to establish the precise cause of pulmonary dysfunction.

Prevalence of sleep apnea and lung function abnormalities in patients with acromegaly.

Background:Sleep apnea (SA) is highly prevalent in acromegaly. Ethnicity influences the prevalence of SA in the general population. We studied the prevalence of SA and other respiratory comorbidities in North Indian patients with active acromegaly.Design:Prospective, observational.Materials and Methods:Consecutive adult patients with active acromegaly (n = 35, age 39.7 ± 13.2 years) and hypersomatotropism (nonsuppression of serum growth hormone after oral glucose and elevated serum insulin-like growth factor-1 [IGF-1]) were evaluated for respiratory symptoms, scoring for SA (Epworth Sleepiness Score [ESS] and STOP-BANG), pulmonary function tests (PFT), high-resolution computerized tomography (HRCT) of the thorax, polysomnography (PSG), and transthoracic echocardiography. Age- and sex-matched healthy individuals (n = 34) served as controls.Results:Acromegaly subjects had dyspnea (34%), cough (37%), excessive daytime somnolence (43%), and fatigue (49%). Clinically significant ESS (>10) and STOP-BANG score (≥3) were present in 41% and 68.6% of subjects, respectively. PFT showed restrictive and obstructive patterns in 45.7% and 11.4% of acromegalics respectively; with higher total lung capacity (TLC), thoracic gas volume (TGV), and residual volume (RV). PSG revealed significantly higher SA events in acromegalics (central [acromegaly 24.63 ± 37.82 vs. control 3.21 ± 5.5], mixed [11 ± 19.46 vs. 3.50 ± 5.96], obstructive [34.86 ± 44.37 vs. 9.71 ± 10.48], and mean apnea-hypopnea index [AHI] [16.91 ± 18.0 vs. 7.86 ± 7.84]). Acromegalics had significantly higher prevalence of obstructive SA (71.4% [mild 31.4%, moderate 20%, severe 20%]) as compared to controls (38.2%). There was no correlation of AHI with serum IGF-1 and disease duration.Conclusion:Acromegaly subjects have a significantly higher prevalence of respiratory symptoms, SA, and abnormalities in PFT. Screening for respiratory comorbidities should be routinely recommended in all patients with acromegaly.

The utility of echocardiography and pulmonary function testing in the preoperative evaluation of pectus excavatum

PurposeEchocardiography (ECHO) and pulmonary function testing (PFT) are routinely performed during the preoperative evaluation of pectus excavatum (PE). We hypothesized that these investigations may be performed selectively based on patient symptoms and pectus severity. MethodsA retrospective review of all PE patients who underwent a Nuss procedure during a 15-year period (2004–2018) was conducted. Symptoms, clinical characteristics, ECHO, and PFT results were extracted from the medical chart. PE severity on computed tomography was measured using the Haller Index (HI) and Correction Index (CI), and reported as mean ± SEM. Logistic and linear regression assessed the ability of symptoms and indices to predict abnormal cardiopulmonary test results. ResultsOf 119 patients, 116 patients had symptom documentation, and 74 (64%) had one or more symptoms. HI and CI were 3.8 ± 1.0 and 31.6 ± 10.3, respectively. Of those with ECHO available (111), 14 (13%) were abnormal, and 12 of 14 required cardiology follow-up. Of those with PFT available (90), the results were abnormal in 15 (17%), including 9 (11%) obstructive, 4 (5%) restrictive, and 2 (2%) mixed. The presence of symptoms did not predict abnormal ECHO or PFT, but each standard deviation increase in the CI was associated with abnormal PFT and ECHO by a factor of 2.2 and 2.0 respectively. HI severity was only associated with ECHO. ConclusionThe rates of abnormal ECHO and PFT testing in PE patients are low, and do not correlate with symptoms. Routine ECHO is still recommended to detect anomalies requiring follow-up. Elevated CI severity may be used to guide selective PFT testing.Levels of evidence: Retrospective Study, Level III

Residual lung damage following ARDS in COVID-19 ICU survivors.

BackgroundCoronavirus disease 2019 acute respiratory distress syndrome (COVID‐19 ARDS) is a disease that often requires invasive ventilation. Little is known about COVID‐19 ARDS sequelae. We assessed the mid‐term lung status of COVID‐19 survivors and investigated factors associated with pulmonary sequelae.MethodsAll adult COVID‐19 patients admitted to the intensive care unit from 25th February to 27th April 2020 were included. Lung function was evaluated through chest CT scan and pulmonary function tests (PFT). Logistic regression was used to identify predictors of persisting lung alterations.ResultsForty‐nine patients (75%) completed lung assessment. Chest CT scan was performed after a median (interquartile range) time of 97 (89–105) days, whilst PFT after 142 (133–160) days. The median age was 58 (52–65) years and most patients were male (90%). The median duration of mechanical ventilation was 11 (6–16) days. Median tidal volume/ideal body weight (TV/IBW) was 6.8 (5.71–7.67) ml/Kg. 59% and 63% of patients showed radiological and functional lung sequelae, respectively. The diffusion capacity of carbon monoxide (DLCO) was reduced by 59%, with a median per cent of predicted DLCO of 72.1 (57.9–93.9) %. Mean TV/IBW during invasive ventilation emerged as an independent predictor of persistent CT scan abnormalities, whilst the duration of mechanical ventilation was an independent predictor of both CT and PFT abnormalities. The extension of lung involvement at hospital admission (evaluated through Radiographic Assessment of Lung Edema, RALE score) independently predicted the risk of persistent alterations in PFTs.ConclusionsBoth the extent of lung parenchymal involvement and mechanical ventilation protocols predict morphological and functional lung abnormalities months after COVID‐19.

Abstract 11594: Deep Learning of the Retina Enables Phenome- and Genome- Wide Analyses of the Microvasculature

Introduction: The retinal fundus is a window for non-invasive assessment of the microvasculature. However, the range of phenotypes and inherited genetic variants associated with the retinal microvasculature remain unknown. Hypothesis: Deep learning of retinal fundus images enables large-scale quantification of vascular indices and an unbiased assessment of phenotypes and genetic variants linked to the microvasculature. Methods: We utilized 97,895 retinal fundus images from 54,813 UK Biobank participants (ages 40-70y, 55% female). Using convolutional neural networks to segment vessels, we calculated vascular branching complexity using fractal dimension (FD), and vascular density, and associated these indices with 1,100 incident ICD-based conditions (median 10y follow-up) and 88 quantitative traits, adjusting for age, sex, smoking status, and ethnicity. Genome-wide association study (GWAS) among 38,932 unrelated individuals was performed. Results: Low retinal vascular FD and density were significantly associated with increased risk of incident hypertension, congestive heart failure, renal failure, type 2 diabetes, sleep apnea, anemia, and multiple ocular conditions. Low retinal vascular FD and density were also linked to quantitative traits including elevated blood pressure, anemia indices, abnormal pulmonary function tests, measures of metabolic disease (high HbA1c, % body fat, BMI), and ocular traits (decreased visual acuity and increased intraocular pressure). GWAS of vascular FD and density identified loci enriched among pathways linked to angiogenesis (VEGF, PDGFR, angiopoietin, and WNT signaling pathways), and inflammation (interleukin, cytokine signaling). Conclusions: Through phenotypic and genotypic analyses, our study showed that the retinal vasculature may serve as a biomarker for future cardiometabolic and ocular disease, and provided insights on genes and biological pathways influencing microvascular indices.

Abnormal Pulmonary Function Testing as an Independent Risk Factor for Procedural Complications During Transthoracic Needle Biopsies.

Computed tomography (CT)-guided transthoracic needle biopsy is an important diagnostic tool for pulmonary nodules, offering a less invasive alternative to surgical procedures. This study aims to better risk stratify patients undergoing this procedure by analyzing the pulmonary function testing (PFT), imaging characteristics, and patient demographics most associated with complications. This retrospective study involved 254 patients undergoing transthoracic needle biopsies at 3 hospitals between October 2016 and December 2019. Demographic data, extent of emphysema, and target lesion characteristics were recorded. Complications were defined as minor (small pneumothorax, mild hemoptysis, or pulmonary hemorrhage) and major (pneumothorax requiring chest tube, hemothorax, rapid atrial fibrillation, or postprocedure hypotension or hypoxia). There were 50 minor (20%) and 18 major complications (7%). As seen with prior studies, older age, increased distance to pleura, and smaller nodule size correlated with an increased risk of complications. Uniquely to our study, emphysema severity, seen on CT (P=0.008) and with decreased forced expiratory volume/forced vital capacity ratio, conferred an increased risk (62.94 vs. 68.74, P=0.05) of complications. Decreased Hounsfield unit of surrounding lung (a surrogate measure of emphysema) and decreased diffusion capacity (11.81 vs. 14.93, P=0.05) were associated with increased risk of major complications. Interestingly, body mass index and comorbidities had no correlation with complications. In addition to previous well-described characteristics, we described physiological data (abnormal PFTs), imaging findings, and nodule location as risk factors of procedural complications. Obtaining preprocedural PFT, in addition to reviewing CT imaging and demographic data, may aid clinicians in better risk stratifying patients undergoing transthoracic needle biopsies.

Association of abnormal pulmonary vasculature on CT scan for COVID-19 infection with decreased diffusion capacity in follow up: A retrospective cohort study.

Coronavirus Disease 2019 (COVID-19) is a respiratory viral illness causing pneumonia and systemic disease. Abnormalities in pulmonary function tests (PFT) after COVID-19 infection have been described. The determinants of these abnormalities are unclear. We hypothesized that inflammatory biomarkers and CT scan parameters at the time of infection would be associated with abnormal gas transfer at short term follow-up. We retrospectively studied subjects who were hospitalized for COVID-19 pneumonia and discharged. Serum inflammatory biomarkers, CT scan and clinical characteristics were assessed. CT images were evaluated by Functional Respiratory Imaging with automated tissue segmentation algorithms of the lungs and pulmonary vasculature. Volumes of the pulmonary vessels that were ≤5mm (BV5), 5-10mm (BV5_10), and ≥10mm (BV10) in cross sectional area were analyzed. Also the amount of opacification on CT (ground glass opacities). PFT were performed 2-3 months after discharge. The diffusion capacity of carbon monoxide (DLCO) was obtained. We divided subjects into those with a DLCO <80% predicted (Low DLCO) and those with a DLCO ≥80% predicted (Normal DLCO). 38 subjects were included in our cohort. 31 out of 38 (81.6%) subjects had a DLCO<80% predicted. The groups were similar in terms of demographics, body mass index, comorbidities, and smoking status. Hemoglobin, inflammatory biomarkers, spirometry and lung volumes were similar between groups. CT opacification and BV5 were not different between groups, but both Low and Normal DLCO groups had lower BV5 measures compared to healthy controls. BV5_10 and BV10 measures were higher in the Low DLCO group compared to the normal DLCO group. Both BV5_10 and BV10 in the Low DLCO group were greater compared to healthy controls. BV5_10 was independently associated with DLCO<80% in multivariable logistic regression (OR 1.29, 95% CI 1.01, 1.64). BV10 negatively correlated with DLCO% predicted (r = -0.343, p = 0.035). Abnormalities in pulmonary vascular volumes at the time of hospitalization are independently associated with a low DLCO at follow-up. There was no relationship between inflammatory biomarkers during hospitalization and DLCO. Pulmonary vascular abnormalities during hospitalization for COVID-19 may serve as a biomarker for abnormal gas transfer after COVID-19 pneumonia.

Pulmonary Function in Long-Term Survivors of Childhood and Adolescence Osteosarcoma: Case Report

Introduction: Chemotherapy used in osteosarcoma have the potential to cause lung damage. The objectives were to analyze lung volumes and capacities, and respiratory muscle strength of patients treated with chemotherapy and surgery for osteosarcoma. The study was designed as a prospective case-series of patients, through the analysis of spirometry, impulse, oscillometry, and manovacuometry tests. Case report: In twenty-one patients, the median age at diagnosis was 15 years, and at inclusion, 30 years. The median disease-free survival time was 10 years. Eight different chemotherapeutic agents were used: cisplatin, doxorubicin, methotrexate, carboplatin, ifophosphamide, epidoxorubicin, cyclophosphamide and etoposide. There were test abnormalities in 14 patients (66.6%), with mild obstructive disorders on spirometry in three patients (14.3%), and obstructive patterns on oscillometry in seven patients (33.3%). On spirometry, the mean ± standard deviation (SD) values of forced vital capacity (FVC) were 91.9%±12.2; for forced expiratory volume in one second (FEV1) were 87.4%±12.2 and FEV1/FVC ratios, 95.4%±7.9. On oscillometry, mean ± SD values for resistance at 5 Hz were 126.2%±36.2; for resistance at 20 Hz, 128.4%±32.4; reactance at 5 Hz, -0.75±0.68 kPa/L/s; for resonant frequency, 15.6±4.2 Hz. Nine patients (42.8%) had reduced maximum pressures on the manovacuometry: Maximum Expiratory Pressure (MEP) were reduced in eight patients, and inspiratory (MIP) in three. The mean ± SD MIP was 89.4±29.5; MEP, 88±37.7. Conclusion: Mild abnormalities in pulmonary function tests in this series of patients were observed years after treatment for osteosarcoma.

EVALUATION OF LUNG FUNCTION AFTER SARS-COV-2 PNEUMONIA

TOPIC: Pulmonary Physiology TYPE: Original Investigations PURPOSE: To investigate the patients' lung function at 3 and 6 months after hospital discharge for Coronavirus Disease 2019 (COVID-19) pneumonia. METHODS: A prospective lung function assessment has been conducted with spirometry measurements, including lung volumes, lung diffusion capacity for carbon monoxide (DLCO) with alveolar volume (VA), and transfer coefficient (KCO) determination. Patients with a restrictive ventilatory defect or impaired DLCO were re-evaluated at 6 months with global spirometry and chest HRCT scan. RESULTS: 40 patients have been enrolled in the study. Among them, 19 (48%) had normal pulmonary function tests (group A), and 21 (52%) showed residual lung function abnormalities at 3 months after hospital discharge (group B). In group B, 4 patients (19%) had an isolated loss of lung volume (Subgroup B1), 13 patients (62%) had both lung volume, and DLCO decreased (Subgroup B2), and 4 patients (19%) had isolated reduction in DLCO (Subgroup B3). At the 6-month follow-up visit, in Subgroup B1, although all patients improved, only one normalized the total lung capacity (TLC). In Subgroup B2, TLC and DLCO increased significantly (p<0.01), but only 3 patients reached normal values. In Subgroup B3, DLCO improved for most patients, normalizing in 50% of them. Always at the 6-months follow-up visit, significant correlations between an internal chest HRCT scan severity score and TLC (r2=0.33;p<0.01) and DLCO (r2=0.32;p<0.01) has been found. CONCLUSIONS: Nearly 50% of patients recovered in the post-critical phase. Most of those with abnormal pulmonary function tests at the 3-months follow-up visit had an improvement at the 6-month evaluation, but only 29% reached normal values. CLINICAL IMPLICATIONS: In patients with previous COVID-19 pneumonia, lung function spontaneous recovery is faster at first. However, at 6-months after hospital discharge, this recovery process goes more slowly, leaving more than one-third of patients with abnormal lung function tests. DISCLOSURES: No relevant relationships by Francesca Cettolo, source=Web Response No relevant relationships by Manuela Ciarfaglia, source=Web Response No relevant relationships by Jordan Franz Giordani, source=Web Response No relevant relationships by Michele Guerini, source=Web Response No relevant relationships by Guido Levi, source=Web Response No relevant relationships by Nicla Orzes, source=Web Response No relevant relationships by Laura Pini, source=Web Response No relevant relationships by Alessandro Pini, source=Web Response No relevant relationships by Claudio Tantucci, source=Web Response No relevant relationships by Silvia Uccelli, source=Web Response

Prevalence and Prognostic Significance of Pulmonary Function Test Abnormalities in Hospitalized Patients With Acute Decompensated Heart Failure With Preserved and Reduced Ejection Fraction.

This study evaluated the prevalence and prognostic impact of lung function abnormalities in patients with acute decompensated heart failure (ADHF) with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF).Methods and Results:Of the 1,012 consecutive patients who were admitted to Nara Medical University with ADHF between 2011 and 2018, 657 routinely underwent spirometry (pulmonary function test [PFT]) before discharge. Lung function was classified as normal or abnormal (restrictive, obstructive, or mixed). Abnormal PFTs were seen in 63.0% of patients with ADHF (36.7%, 13.1%, and 13.2% for restrictive, obstructive, and mixed, respectively). The prevalence of abnormal PFT increased with age (P<0.001). Overall, abnormal PFT was an independent predictor of the composite endpoint of cardiovascular mortality or hospitalization for HF (adjusted hazard ratio [HR] 1.402; 95% confidence interval [CI] 1.039-1.914; P=0.027). Abnormal PFT (adjusted HR 2.294; 95% CI 1.368-4.064; P=0.001), as well as the restrictive (HR 2.299; 95% CI 1.322-4.175; P=0.003) and mixed (HR 2.784; 95% CI 1.399-5.581; P=0.004) patterns, were predictive of the composite endpoint in HFpEF, but not in HFrEF. Abnormal PFT was prevalent and associated with poor outcomes in ADHF. Spirometry may be a useful tool in patients with ADHF, especially in those with HFpEF, to identify those at higher risk of a poorer outcome.

A prospective evaluation of lung function at three and six months in patients with previous SARS-COV-2 pneumonia

ObjectiveThis study investigated the consequences of Coronavirus Disease 2019 (COVID-19) pneumonia on lung function in the first 6 months after hospital discharge. MethodsA prospective lung function assessment in SARS-CoV2 patients with COVID-19 pneumonia, hospitalized between March and April 2020, was conducted with spirometry measurements including lung volumes, mainly total lung capacity (TLC), lung diffusion capacity for carbon monoxide (DLCO) collected at 3 months after hospital discharge. Patients with restrictive ventilatory defect or impaired DLCO or both were re-evaluated at 6 months with global spirometry and chest HRCT scan. ResultsAmong 40 consecutive patients, 19 (48%) had normal pulmonary functional tests (group A), and 21 (52%) showed residual lung function abnormalities at 3 months after hospital discharge (group B). In group B, 4 patients (19%) had only loss of lung volume as shown by TLC reduction (group 1), 13 patients (62%) had decreased both TLC and DLCO (group 2), and 4 patients (19%) had isolated reduction in DLCO (group 3). At 6-month follow-up in group 1, although all patients improved, only one normalized total lung capacity (TLC). In group 2, TLC and DLCO increased significantly (p < 0.01), but only 3 patients reached normal values. In group 3, DLCO improved for most patients, normalizing in 50% of them. At 6-months significant correlations between an internal-built chest HRCT scan severity score and TLC (r2 = 0.33; p < 0.01) and DLCO (r2 = 0.32; p < 0.01) were found. ConclusionsNearly 50% of patients recovered in the post-critical phase. Most of those with abnormal pulmonary function tests at 3 months improved subsequently, but only another 29% (6 out of 21) reached normal values at 6 months. These results indicate that lung function spontaneous recovery is faster at first and occurs more slowly thereafter, leaving more than one third (15 out of 40) of patients with abnormal lung function tests at 6 months.

The effect of iron overload on pulmonary function tests in children with thalassemia major

Objective The aim was to determine pulmonary function abnormalities in children with thalassemia major (TM) and assess the relation between these abnormalities and iron overload. Introduction Regular blood transfusion program is among the most important factors that help in improving the survival of patients with TM; however, it leads to iron deposition in many organs such as lung. Most studied concerned about effect of iron on lung functions, revealed abnormalities, but limited data were observed. Patients and methods This cross-sectional study had included 50 children aged between 6 and 18 years (34 males and 16 females) with TM. All included children were subjected to full clinical examination and laboratory investigations including complete blood counts and serum ferritin. Pulmonary function tests (PFTs) were assessed in all included children using spirometry. Results Overall, 82% of the study group had abnormal pattern of PFTs. The majority of them were restrictive and of mild severity. Moreover, serum ferritin levels were found to be significantly higher in patients with thalassemia with abnormal PFTs (1456.65 ± 650.39) than patients with thalassemia with normal PFTs (744.34 ± 541.27) (P = 0.03). Conclusion Most children involved in the study had abnormal pattern of PFTs, and most frequent abnormality is restrictive pattern. In addition, there was a strong relationship between serum ferritin level and lung affection.

Ventilatory limitations are not associated with dyspnea on exertion or reduced aerobic fitness in pectus excavatum.

Exercise intolerance and chest pain are common symptoms in patients with pectus excavatum. To assess if the anatomic extent of pectus deformities determined by the correction index (CI) is associated with a pulmonary impairment at rest and during exercise we performed a retrospective review on pectus patients in our center who completed a symptom questionnaire, cardiopulmonary exercise test (CPET), pulmonary function tests (PFT), and chest magnetic resonance imaging. Of 259 patients studied, dyspnea on exertion and chest pain was reported in 64% and 41%, respectively. Peak oxygen uptake (VO2 ) was reduced in 30% and classified as mild in two-thirds. A pulmonary limitation during exercise was identified in less than 3%. Ventilatory limitations on PFT was found in 26% and classified as mild in 85%. Obstruction was the most common abnormal pattern (11%). There were no differences between patients with normal or abnormal PFT patterns for the CI, VO2, or percentage reporting dyspnea or chest pain. Scatter plots demonstrated significant but weak inverse relationships between the CI and lung volumes at rest and during exercise. Multivariable linear regression modeling evaluating predictors of VO2 demonstrated positive associations with the forced expiratory volume at one second and a negative association with the CI. We conclude that resting PFT patterns have poor correlation with the anatomic extent of the pectus defect, symptomatology or aerobic fitness. Pulmonary limitations on CPET are uncommon and lung volumes during exercise are only minimally associated with the CI.

Increased Rate of Pulmonary Toxicity in Pediatric Patients with Relapsed Hodgkin Lymphoma Receiving Brentuximab Vedotin

*Kelly E Faulk and Jenna Sopfe contributed equally to this work and are considered co-first authors.Background: In pediatric patients with relapsed or refractory Hodgkin lymphoma, intensification of conventional chemotherapy and radiation has shown limited success with high rates of treatment-associated morbidity and highlighted the need for alternative, targeted approaches in this high-risk population. Brentuximab vedotin (Bv) is an anti-CD30 monoclonal antibody-drug conjugated to monomethyl auristatin E that has improved outcomes and reduced toxicity compared to standard salvage regimens. It is now approved for use in relapsed or refractory Hodgkin lymphoma and several ongoing pediatric clinical trials are underway to test the effectiveness of Bv as frontline therapy. In the existing literature, acute pulmonary toxicity has been described in adults with Bv but typically in the setting of concurrent administration with bleomycin, whereas the incidence of lung toxicity attributed to Bv alone has been reported at only 5% (Moskowitz 2015). There is little published data on lung toxicity of Bv in pediatric patients. This study aims to evaluate the prevalence of acute pulmonary toxicity among pediatric and young adult relapsed Hodgkin lymphoma patients and define risk factors for this complication, specifically examining the association of Bv with pulmonary toxicity when adjusting for other exposures.Methods: We performed a retrospective cohort study of relapsed or refractory Hodgkin lymphoma patients who were originally diagnosed from 2006-2016 and treated at Children's Hospital Colorado. We examined demographic, clinical and treatment characteristics among patients who developed acute pulmonary toxicity (defined as hypoxemia, dyspnea or radiographic pneumonitis of ≥ grade 3 and/or newly abnormal pulmonary function testing occurring at any time from initiation of relapse therapy until 6 months off therapy) to determine potential risk factors. A Fisher's exact test was used to determine the statistical significance in the difference of the primary outcome (pulmonary toxicity) for those exposed and not exposed to Bv. Univariate and multivariate logistic regression modeling was performed to evaluate the association of Bv with pulmonary toxicity, adjusting for cumulative bleomycin and pulmonary radiation dose received as well other risk factors identified in univariate analysis.Results : We identified 22 patients, age 6-24 years (median 15) at time of initial diagnosis, who underwent treatment at our institution. Twelve (52.2%) were male. Nine patients (40.9%) received Bv as a component of their relapse therapy regimen. On preliminary analysis, acute pulmonary toxicity was seen in 6 patients (27.3%). There was a statistically significant difference in pulmonary toxicity among patients who received Bv compared to patients who did not receive Bv (p=0.023); of patients who received Bv, 5/9 (55.6%) experienced acute pulmonary toxicity, compared to 1/13 (7.7%) patient who did not receive Bv. Further analyses of additional risk factors and calculation of odds ratios, adjusted for bleomycin and radiation exposure, are forthcoming.Conclusions: At our institution, the administration of Bv in pediatric and young adult patients with relapsed or refractory Hodgkin lymphoma is associated with a higher rate of acute pulmonary toxicity than has previously been reported. Ongoing analysis will examine the magnitude of risk associated with Bv and the interaction of other known risk factors. As investigation into the use of Bv continues, this emerging safety and toxicity profile data will be important in understanding the risk of pulmonary toxicity and ensuring appropriate monitoring. DisclosuresNo relevant conflicts of interest to declare.

Hyperinflation is associated with increased respiratory rate and is a more sensitive measure of cystic fibrosis lung disease during infancy compared to forced expiratory measures.

The goal of this study was to identify clinical features associated with abnormal infant pulmonary function tests (iPFTs), specifically functional residual capacity (FRC), in infants with cystic fibrosis (CF) diagnosed via newborn screen (NBS). We hypothesized that poor nutritional status in the first 6-12 months would be associated with increased FRC at 12-24 months. This study utilized a combination of retrospectively and prospectively collected data from ongoing research studies and iPFTs performed for clinical indications. Demographic and clinical features were obtained from the electronic medical record. Forced expiratory flows and volumes were obtained using the raised volume rapid thoracoabdominal technique (RVRTC) and FRC was measured via plethysmography. A total of 45 CF NBS infants had iPFTs performed between 12 and 24 months. Mean forced vital capacity, forced expiratory volume in 0.5 s, and forced expiratory flows were all within normal limits. In contrast, the mean FRC z-score was 2.18 (95% confidence interval [CI] = 1.48, 2.88) and the mean respiratory rate (RR) z-score was 1.42 (95% CI = 0.95, 1.89). There was no significant association between poor nutritional status and abnormal lung function. However, there was a significant association between higher RR and increased FRC, and a RR cutoff of 36 breaths/min resulted in 92% sensitivity to detect hyperinflation with 32% specificity. These results suggest that FRC is a more sensitive measure of early CF lung disease than RVRTC measurements and that RR may be a simple, noninvasive clinical marker to identify CF NBS infants with hyperinflation.

POS0250 SIGNIFICANT DAMAGE OCCURS EARLY IN THE COURSE OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS AND IS MAINLY DUE TO DISEASE-RELATED SEQUELAE

Background:Following the introduction of effective immunosuppressive treatments, ANCA-associated vasculitides (AAV) have become chronic diseases with a remitting-relapsing course. Therefore, preventing chronic damage accrual during follow-up is critical, as relapses, treatment-related side effects, and comorbidities may significantly affect the long-term outcomes of AAV patients. At present, no study specifically evaluated the burden of damage in patients with eosinophilic granulomatosis with polyangiitis (EGPA).Objectives:To describe short-term (6 months) and long-term (5 years) damage accrual in patients with newly diagnosed EGPA.Methods:Patients diagnosed with EGPA, according to ACR criteria and/or Chapel Hill definitions and regularly followed-up in our vasculitis center for ≥5 years were included. Damage accrual was assessed with the Vasculitis Damage Index (VDI). Short-term and long-term damage accrual was defined by VDI at 6 months and at 5 years, respectively, and categorized as related to vasculitis or its treatment.Results:VDI data at 6 months were available for 45 EGPA patients: 24 (53.3%) female, mean age at diagnosis 51.6±13.0 years. ANCA were positive in 17 patients (37.8%), with MPO being the only detected enzyme immunoassay (EIA)-specificity. At 6 months mean VDI was 2.8±1.3; 25/45 (55.6%) and 6/45 patients (13.3%) presented ≥3 and ≥5 items, respectively, whilst only 1 patient (2.2%) showed no items of damage. VDI data at 5 years were available for 32/45 EGPA patients (71.1%): 16 (50%) female, mean age at diagnosis 51.5±13.1 years. MPO-ANCA were positive in 13 patients (40.6%). At 5 years mean VDI was 3.5±1.3, with 26/32 (81.3%) and 7/32 patients (21.9%) presenting ≥3 and ≥5 items, respectively; notably, no patients presented a VDI=0 at 5 years.The most frequent disease-related VDI items at 6 months and at 5 years were asthma, chronic sinusitis, peripheral neuropathy, cardiomyopathy, pulmonary function tests abnormalities and nasal blockage (Figure 1). Osteoporotic fractures, diabetes and systemic hypertension were the most commonly reported treatment-related items at 6 months and at 5 years (Figure 1). Damage accrual progressively rose during the 5-year follow-up (P=0.023), mainly due to disease-related items rather than treatment-related items both at 6 months (disease related VDI 2.6±1.2, treatment-related VDI 0.3±0.6) and at 5 years (disease related VDI 2.9±1.2, treatment-related VDI 0.6±0,7). No significant difference in terms of damage accrual was observed between ANCA-positive and ANCA-negative patients (P &gt;0.5).Conclusion:In our cohort of EGPA patients damage accrual occurs early, with more than half of the patients displaying ≥3 VDI items already at 6 months. Poor control of previous disease activity, particularly ENT and respiratory manifestations, contributes to progressive damage accrual more than treatment side effects.Figure 1.Disease-related and treatment-related VDI items at 6 months and at 5 years in patients with EGPA.Disclosure of Interests:None declared

Integrative respiratory follow-up of severe COVID-19 reveals common functional and lung imaging sequelae

BackgroundCOVID-19 pandemic resulted in an unprecedented number of hospitalizations in general wards and intensive care units (ICU). Severe and critical COVID-19 patients suffer from extensive pneumonia; therefore, long-term respiratory sequelae may be expected. Research questionWe conducted a cohort study to determine respiratory sequelae in patients with severe and critical COVID-19. We aimed at evaluating the proportion of patients with persisting respiratory symptoms and/or abnormalities in pulmonary function tests (PFT) or in lung imaging. Study designand methods: This is a single center cohort study including COVID-19 survivors who underwent a three-month follow-up with clinical evaluation, PFT and lung high-resolution computed tomography (HRCT). All clinical, functional, and radiological data were centrally reviewed. Multiple linear regression analysis was performed to identify factors associated with residual lesions on HRCT. ResultsFull clinical evaluation, PFT and lung HRCT were available for central review in 126, 122 and 107 patients, respectively. At follow-up, 25% of patients complained from dyspnea and 35% from fatigue, lung diffusion capacity (DLCO) was decreased in 45%, 17% had HRCT abnormalities affecting more than 5% of their lung parenchyma while signs of fibrosis were found in 21%. In multiple linear regression model, number of days in ICU were related to the extent of persisting lesions on HRCT, while intubation was associated with signs of fibrosis at follow-up (P = 0.0005, Fisher's exact test). In contrast, the severity of lung imaging or PFT changes were not predictive of fatigue and dyspnea. InterpretationAlthough most hospitalized COVID-19 patients recover, a substantial proportion complains from persisting dyspnea and fatigue. Impairment of DLCO and signs suggestive of fibrosis are common but are not strictly related to long-lasting symptoms.

Radiological and functional lung sequelae of COVID-19: a systematic review and meta-analysis

BackgroundThe coronavirus disease 2019 (COVID-19) causes a wide spectrum of lung manifestations ranging from mild asymptomatic disease to severe respiratory failure. We aimed to clarify the characteristics of radiological and functional lung sequelae of COVID-19 patients described in follow-up period.MethodPubMed and EMBASE were searched on January 20th, 2021 to investigate characteristics of lung sequelae in COVID-19 patients. Chest computed tomography (CT) and pulmonary function test (PFT) data were collected and analyzed using one-group meta-analysis.ResultsOur search identified 15 eligible studies with follow-up period in a range of 1–6 months. A total of 3066 discharged patients were included in these studies. Among them, 1232 and 1359 patients were evaluated by chest CT and PFT, respectively. The approximate follow-up timing on average was 90 days after either symptom onset or hospital discharge. The frequency of residual CT abnormalities after hospital discharge was 55.7% (95% confidential interval (CI) 41.2–70.1, I2 = 96.2%). The most frequent chest CT abnormality was ground glass opacity in 44.1% (95% CI 30.5–57.8, I2 = 96.2%), followed by parenchymal band or fibrous stripe in 33.9% (95% CI 18.4–49.4, I2 = 95.0%). The frequency of abnormal pulmonary function test was 44.3% (95% CI 32.2–56.4, I2 = 82.1%), and impaired diffusion capacity was the most frequently observed finding in 34.8% (95% CI 25.8–43.8, I2 = 91.5%). Restrictive and obstructive patterns were observed in 16.4% (95% CI 8.9–23.9, I2 = 89.8%) and 7.7% (95% CI 4.2–11.2, I2 = 62.0%), respectively.ConclusionsThis systematic review suggested that about half of the patients with COVID-19 still had residual abnormalities on chest CT and PFT at about 3 months. Further studies with longer follow-up term are warranted.