Complete Pulmonary Function Tests Research Articles

RESPIRATORY SEQUELAE AND ASSOCIATED RISK FACTORS AMONG PATIENTS WITH COVID-19 SIX MONTHS AFTER HOSPITAL DISCHARGE

TOPIC: Chest Infections TYPE: Late Breaking PURPOSE: Patients hospitalized with coronavirus disease 2019 (COVID-19) have demonstrated impairments in lung function after discharge. The most commonly documented abnormalities include reductions in diffusion capacity for carbon monoxide (DLCO), total lung capacity (TLC), and impairments in six-minute walk testing (6MWT). It is important to identify risk factors for prolonged pulmonary dysfunction following COVID-19 so that physicians may more equitably direct follow-up resources in their communities. METHODS: Patients hospitalized at the University of Virginia Medical Center with COVID-19 received a phone call after discharge in which they underwent a 10-point symptom-based questionnaire. Those who had persistent respiratory symptoms were invited to follow up for pulmonary function testing; including spirometry, lung volumes, diffusion capacity, and exercise tolerance. Of the 234 patients who received a screening phone call, 123 completed pulmonary function testing at 6 months. A multivariate analysis was performed to assess risk factors for prolonged lung function impairment. A total of 12 covariates, including the severity of COVID-19 infection, smoking history, history of pulmonary disease, sex, ethnicity, body mass index (BMI), age, highest recorded d-dimer, highest recorded ferritin, highest recorded c-reactive protein, clinically relevant venothromboembolism and need for oxygen at discharge were included in the analysis. RESULTS: At a mean follow-up time of 174 days, 31% of patients demonstrated newly developed impairments in diffusion capacity, 27% had new impairments in lung volumes and 36% had new abnormalities in spirometry. Impairments in lung function correlated significantly with smoking status (never smoker OR = 0.39; CI 0.17-0.88), sex (male sex OR = 2.67; CI 1.09-7.1) and age (OR 1.04; CI 1.01-1.08). Of note, COVID-19 severity, as measured by the National Institute of Health (NIH) COVID-19 illness severity scale and the World Health Organization (WHO) ordinal scale, was not significantly associated with long-term lung function outcomes. CONCLUSIONS: Long-term impairments in lung function following COVID-19 are common, occurring in roughly 30% of patients, and include abnormalities in diffusion capacity, lung volumes and spirometry. Long-term impairments in lung function are directly associated with smoking status, male sex, and older age. Surprisingly, long-term lung function does not appear to correlate with COVID-19 severity as measured by the NIH COVID-19 illness severity scale and the WHO ordinal scale. CLINICAL IMPLICATIONS: Patients who are at higher risk for impairments in lung function following COVID-19 include those with a history of smoking, male sex, and older age. Particular attention should be paid to these populations when determining how to best allocate community follow-up resources. DISCLOSURES: No relevant relationships by Carissa Harnish-Cruz, source=Web Response No relevant relationships by Alex Kadl, source=Web Response No relevant relationships by Samuel Konkol, source=Web Response no disclosure on file for David Martin; No relevant relationships by Kelsie Mietla, source=Web Response No relevant relationships by CHINTAN RAMANI, source=Web Response No relevant relationships by Ryan Sessums, source=Web Response No relevant relationships by John Widere, source=Web Response

Performance of Lung Ultrasound for Monitoring Interstitial Lung Disease.

In this study, we sought to assess the validity of lung ultrasound (LUS) during the follow-up of patients with a wide spectrum of interstitial lung diseases (ILDs). Twenty-four patients (13 males, 11 females; mean age ± SD, 65.4 ± 14.3 years; age range, 40-84 years) with a diagnosis of ILDs who were admitted to the Interstitial Lung Disease Unit were prospectively enrolled. Patients were examined with a 56-lung intercostal space LUS protocol in lateral decubitus position, at baseline, 6-months, and 1-year. The LUS score was defined as the sum of B-lines counted in each intercostal space. All patients underwent complete pulmonary function tests at baseline and follow-up time-points. High-resolution computed tomography (HRCT) was performed at baseline and during follow-up, according to personalized patients' needs. All HRCT studies were graded according to the Warrick scoring system (WS). Pooled data analysis showed a significant correlation between WS and LUS scores (P< .001). For separate time-point analysis, a significant correlation between LUS scores and WS was found at baseline (P< .001) and 1 year (P= .005). LUS scores negatively correlated with alveolar volume (VA) (P< .046) and diffusing capacity for carbon monoxide (DLCO) (P< .001) at 6 months and with transfer coefficient of the lung for carbon monoxide (KCO) (P< .031) and DLCO (P= .002) at 12-months. A multivariate regression model showed DLCO to be an independent predictor of LUS score at 1 year (P= .026). Our results highlight the validity and potential applicability of LUS for disease monitoring in a wide spectrum of ILDs.

Z-alpha1-antitrypsin polymers and small airways disease: a new paradigm in alfa-1 anti-trypsin deficiency-related COPD development?

The presence of Alpha1-Antitrypsin (AAT) polymers, known to promote a sustained pro-inflammatory activity, has been previously demonstrated in bronchial biopsies of subjects with Z-AAT deficiency (AATD) suggesting a possible role in the development of COPD through a small airway disease impairment. The study aimed to assess the presence of small airways dysfunction and the potential correlation with the presence of Z-AAT polymers obtained by Exhaled Breath Condensate (EBC) collection in PiZZ subjects, as compared with matched healthy PiMM subjects. We enrolled 19 asymptomatic, never smoker subjects: 9 PiZZ and 10 PiMM as controls, without obstructive ventilatory defect (i.e., normal FEV1/VC% ratio). All subjects underwent complete pulmonary function tests (PFT). EBC was collected in all subjects. ELISA test was applied to search for Z-AAT polymers. The PiZZ subjects showed normal lung volumes and DLCO values. However, in comparison with PiMM subjects, the single breath test N2 wash-out revealed significant differences regarding the phase III slope (1.45±0.35 N2/L vs. 0.96±0.40 N2/L) (p<0.02) in the PiZZ subjects, while the closing volume/vital capacity ratio (14.3±4.5 % vs. 11.3±6.3 %) was not significantly increased. The ELISA test detected the presence of Z-AAT polymers in 44% of PiZZ patients. Asymptomatic, never smoker PiZZ subjects with normal spirometry and lung diffusion capacity showed airways impairment when compared to PiMM subjects. Although Z-AAT polymers were found only in 44% of PiZZ subjects, these findings suggest the possibility that chronic bronchiolitis can develop as a result of the long-term pro-inflammatory activity of Z-AAT polymers in subjects with Z-related AATD.

Quality of life and lung function after pleurectomy/decortication for malignant pleural mesothelioma.

Impact of pleurectomy/decortication (P/D) on quality of life (QOL) is not widely reported. We investigated QOL and lung function after P/D. A single-centre, retrospective cohort study was performed among patients who underwent P/D for malignant mesothelioma between June 2014 and June 2018 at Hyogo College of Medicine. Data at 4 points before and 3, 6 and 12 months on QOL and lung function were evaluated with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and pulmonary function tests. Forty-five out of 65 patients completed SF-36. Physical function and role physical decreased from 78 to 65 and 69 to 41 and did not recover. Body pain decreased from 74 to 52. It increased to 62 at 12 months but was lower than before. General health perceptions, vitality and social function decreased from 56 to 49, 50 to 47 and 63 to 50, respectively, but returned to baseline. Role emotional decreased from 75 to 54, then once increased to 63, but decreased again to 58. Mental health tended to improve from 58 to 70. Thirty-eight patients out of 45 completed pulmonary function tests. Forced vital capacity and forced expiratory volume in 1 s decreased from 98% to 61% and 93% to 67% and did not increase. Right-sided surgery or complications was the risk factors of poor lung function but no significant risk factors in QOL. This study suggests that P/D had an impact on QOL. Despite the lack of recovery in lung function QOL in mental aspects tended to improve, suggesting that pulmonary function tests alone are limited in assessing QOL.

Ultrasound Shear Wave Elastography for Evaluation of Diaphragm Stiffness in Patients with Stable COPD: A Pilot Trial

Skeletal muscle dysfunction is one of the most common comorbidities in chronic obstructive pulmonary disease (COPD). The occurrence of respiratory failure in COPD is common and leads to the patient's death. The diaphragm is the most important muscle in the respiratory system and plays a key role in the onset of respiratory failure. This study explores the feasibility of ultrasound shear wave elastography (SWE) to measure diaphragmatic stiffness and evaluates its changes in COPD patients. In total, 77 participants (43 patients with stable COPD and 34 healthy controls) were enrolled. All subjects underwent complete diaphragmatic ultrasound SWE measurements and pulmonary function tests. The diaphragmatic stiffness was indicated via diaphragmatic shear wave velocity (SWV) at functional residual capacity (FRC). A trained operator performed the ultrasound SWE examinations of the first 15 healthy controls thrice to assess the reliability of diaphragmatic SWE. A good to excellent reliability was found in diaphragmatic SWV at FRC (ICC = 0.93, 95%CI 0.82-0.98). As compared to the control group, the diaphragmatic SWV at FRC was considerably high in the COPD group (median 2.5 m/s versus 2.1 m/s, P = .008). Diaphragmatic SWV at FRC was linked to forced expiratory volume in one second (r = -0.30, P = .009), forced vital capacity (r = -0.33, P = .003), modified Medical Research Council score (r = 0.30, P = .001), and COPD assessment test score (r = 0.48, P < .001). Ultrasound SWE may be employed as an effective tool for quantitative evaluation of diaphragm stiffness and can help in personalized management of COPD, such as treatment guidance and follow-up monitoring.

Allergic-like disorders and asthma in patients with common variable immunodeficiency: a multi-center experience

Objective Common variable immune deficiency (CVID) encompasses a variety of diseases characterized by disturbed immunoglobulin (Ig) production and various immune dysregulations. Scarce data are available regarding relationships between CVID and allergic diseases. Here we examined possible associations between allergies and CVID. Methods For this multicenter study, we prospectively enrolled 79 adult CVID patients (≥18 years) who were diagnosed and treated between 2002–2017 at the Hadassah-Hebrew University and Shaare Zedek Medical Centers, Jerusalem, Israel. These patients were examined for allergic manifestations. Patient evaluation comprised medical history, physical examination, skin allergen testing, complete blood count, serum immunoglobulins, IgE levels, and pulmonary function tests. Results After implementing exclusion criteria, 29 patients were included in the final analysis. Allergic-like disorders were diagnosed in 65% of CVID patients with non-elevated serum IgE levels. Moreover, allergic CVID patients exhibited a higher prevalence of bronchiectasis on chest CT. Autoimmunity was diagnosed in 41.3% of CVID subjects. The type I allergy detected in our study was non-IgE mediated. Conclusions Timely diagnosis and stratification of allergy in CVID patients is expected to improve their outcome and quality of life, as well as promote appropriate treatment and better management of pulmonary exacerbations.

Limitations of Applying the Hematopoietic Cell Transplantation Comorbidity Index in Pediatric Patients Receiving Allogeneic Hematopoietic Cell Transplantation

Identifying which patients are at high risk for transplant-related mortality, prior to allogeneic hematopoietic cell transplantation (alloHCT), is crucial both to guide decision making with patients and families and to inform the alloHCT approach. There is a paucity of data evaluating the utility of the HCT comorbidity index (HCT-CI) in pediatric patients. We performed a retrospective cohort study of 188 patients who underwent alloHCT between January 2008 and October 2016 and assessed pretransplant comorbidities defined and weighted by the HCT-CI. The primary endpoint of our study was overall survival (OS). Kaplan-Meier method was used to assess survival estimates at 1-year post-transplant and did not differ based on HCT-CI scores: 78.7% (SE 6.69%) for HCT-CI=0, 74.7% (SE 6.33%) for HCT-CI=1 to 2, and 77.3% (SE 4.17%) for HCT-CI ≥3. Multivariable Cox proportional hazards analysis did not show HCT-CI having an effect on OS: hazard ratio (HR) of 0.633 (95% confidence interval [CI], 0.297 to 1.347) for HCT-CI scores 1 to 2 and HR of 0.935 (95% CI, 0.456 to 1.918) for HCT-CI scores ≥3 compared to scores of 0. The most frequent comorbidities observed were hepatic disease (mild in 29%, severe in 23%) and pulmonary disease (moderate in 15% and severe in 29%). However, only 55% were able to complete pulmonary function testing. Hepatic disease was based on transaminitis in 48% and by bilirubin alone in 26% of patients; 46% of patients with hepatic dysfunction had an underlying hemoglobinopathy and hyperbilirubinemia related to ongoing hemolysis. This study evaluates HCT-CI comorbidities in greater detail than has been performed previously in children undergoing alloHCT. We identify challenges with the HCT-CI in the pediatric population and highlight the comorbidities that may benefit from adjustments to their definition to create an improved risk assessment tool for children.

Pitfalls in Expiratory Flow Limitation Assessment at Peak Exercise in Children: Role of Thoracic Gas Compression.

Thoracic gas compression and exercise-induced bronchodilation can influence the assessment of expiratory flow limitation (EFL) during cardiopulmonary exercise tests. The purpose of this study was to examine the effect of thoracic gas compression and exercise-induced bronchodilation on the assessment of EFL in children with and without obesity. Forty children (10.7 ± 1.0 yr; 27 obese; 15 with EFL) completed pulmonary function tests and incremental exercise tests. Inspiratory capacity maneuvers were performed during the incremental exercise test for the placement of tidal flow volume loops within the maximal expiratory flow volume (MEFV) loops, and EFL was calculated as the overlap between the tidal and the MEFV loops. MEFV loops were plotted with volume measured at the lung using plethysmography (MEFVp), with volume measured at the mouth using spirometry concurrent with measurements in the plethysmograph (MEFVm), and from spirometry before (MEFVpre) and after (MEFVpost) the incremental exercise test. Only the MEFVp loops were corrected for thoracic gas compression. Not correcting for thoracic gas compression resulted in incorrect diagnosis of EFL in 23% of children at peak exercise. EFL was 26% ± 15% VT higher for MEFVm compared with MEFVp (P < 0.001), with no differences between children with and without obesity (P = 0.833). The difference in EFL estimation using MEFVpre (37% ± 30% VT) and MEFVpost (31% ± 26% VT) did not reach statistical significance (P = 0.346). Not correcting the MEFV loops for thoracic gas compression leads to the overdiagnosis and overestimation of EFL. Because most commercially available metabolic measurement systems do not correct for thoracic gas compression during spirometry, there may be a significant overdiagnosis of EFL in cardiopulmonary exercise testing. Therefore, clinicians must exercise caution while interpreting EFL when the MEFV loop is derived through spirometry.

SMALL AIRWAYS DISEASE AND Z-ALPHA1-ANTITRYPSIN POLYMERS: IS THERE A CORRELATION?

SESSION TITLE: Late-breaking Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: The aim of the study was to assess the presence of small airways dysfunction and the potential correlation with the presence of Z-AAT polymers obtained by Exhaled Breath Condensate (EBC) collection in PiZZ subjects, comparing with matched healthy PiMM subjects. METHODS: We enrolled 17 asymptomatic non-smoker subjects: 9 PiZZ and 8 PiMM as controls, without obstructive ventilatory defect (i.e.: normal FEV1/VC ratio). All subjects underwent complete pulmonary function tests (PFT). EBC was collected in PiZZ patients. ELISA test was applied to search for Z-AAT polymers. RESULTS: The PiZZ subjects showed normal lung volumes and DLCO values. However, In comparison with PiMM subjects, the single breath test N2 wash-out revealed significant differences regarding the phase III slope (1.5±0.4 N2/L vs 1.1±0.3 N2/L) and the closing volume/vital capacity ratio (14.3±4.5 % vs 9.5±5.3 %) (p<0.05) in the PiZZ subjects. The ELISA test detected the presence of Z-AAT polymers in 4 PiZZ patients. No correlations were found between polymers levels and any functional respiratory parameter. CONCLUSIONS: PiZZ subjects showed small airways dysfunction when compared to PiMM subjects. Surprisingly, Z-AAT polymers were found only in 4 PiZZ subjects; this is probably due to the sample methodology. New studies are needed to evaluate the correlation between bronchial Z-AAT polymers and small airway impairment in subjects with Z-AAT deficiency. CLINICAL IMPLICATIONS: The presence of Alpha1-Antitrypsin (AAT) polymers that are pro-inflammatory has been previously demonstrated in bronchial biopsies of subjects with Z-AAT deficiency (Respir Res, 2014 Sep 14;15:112), suggesting a possible role in the development of COPD. DISCLOSURES: No relevant relationships by Marianna Arici, source=Web Response No relevant relationships by Jordan Franz Giordani, source=Web Response No relevant relationships by Guido Levi, source=Web Response No relevant relationships by Laura Pini, source=Web Response No relevant relationships by Chiara Rocchetti, source=Web Response No relevant relationships by Claudio Tantucci, source=Web Response No relevant relationships by Laura Tiberio, source=Web Response

Does thoracoplasty adversely affect lung function in complex pediatric spine deformity? A 2-year follow-up review.

Retrospective review of prospective multi-center cohort. To investigate the impact of thoracoplasty on pulmonary function at 2-year follow-up among complex pediatric spine deformity patients. Complex pediatric spine deformities may be associated with significant rib prominence causing body image concerns. Surgical correction of spine deformity may include thoracoplasty to correct the rotational prominence. Some surgeons refrain from performing thoracoplasty due to its purported negative effect on pulmonary function. There is paucity of literature on the effect of thoracoplasty on pulmonary function at 2-year follow-up in pediatric patients with complex spine deformity. We reviewed data of 312 patients (> 100°, with or without vertebral column resection (VCR)) or (< 100° with VCR)) from an international multicenter database. Data of 106 patients with complete radiographic and pulmonary function test (PFT) assessment with a minimum of 2-year follow-up was analyzed. Paired t test was performed to compare pre-op and 2-year PFT results. PFT comparison was stratified based on thoracoplasty status (thoracoplasty: Group 1 vs. no thoracoplasty: Group 2). 106 patients (61 patients Group 1 vs. 45 in Group 2). The average age and gender ratio were similar in both groups (p > 0.05). Group 1 had significantly lower body mass index (BMI) compared to Group 2 (18.4kgm-2 ± 2.8 vs. 19.9kgm-2 ± 4.8, p = 0.0351). The average baseline coronal and sagittal Cobbs were larger for Group 1 relative to Group 2 (p <0.05). The distribution of deformity etiology and curve types, and apices were similar between the two groups (p > 0.05). The rate of pre-op utilization of halo gravity traction (HGT) was 52.5% vs. 26.7% (p = 0.008), at an average duration of 103days vs. 47days, p = 0.0001. The rate of surgical osteotomies was similar in both groups. Estimated blood volume (EBV) loss was greater in Group 1 (63.1% vs. 43.1%, p = 0.0012). Post-op coronal and sagittal Cobb correction was similar in both groups. The incidence of post-op pulmonary complication was similar in both groups (8.2% vs. 8.9%, p = 0.899). Baseline and 2-year follow-up PFT did not differ significantly between and within the groups. Vertebral column resection (VCR) did not negatively affect PFT in both groups. Despite higher curve magnitudes in patients undergoing surgical correction and thoracoplasty for complex pediatric spine deformity, our findings revealed that thoracoplasty does not negatively affect pulmonary function at 2-year follow-up.

Cardiopulmonary Status in Adults with Osteogenesis Imperfecta: Intrinsic Lung Disease May Contribute More Than Scoliosis

Osteogenesis imperfecta (OI) is a heterogeneous group of collagen-related disorders characterized by osteopenia, bone fractures, spine deformities, and nonskeletal complications. Cardiopulmonary complications are the major cause of morbidity and mortality in adults with OI. The cause of such problems was often attributed solely to the presence of large scoliosis curves affecting pulmonary function and, indirectly, cardiovascular health. However, recent studies suggest this may not be the case. Therefore, determining the relationships and causative agents of cardiopulmonary problems in patients with OI, specifically pulmonary impairment, is important to improving the overall wellbeing, quality of life, and survival of these patients. (1) Is cardiopulmonary fitness in OI solely related to the presence of scoliosis? (2) What is the prevalence of heart and lung complications in this adult population? (3) Does the presence of pulmonary impairment impact quality of life in adults with OI? This is a prospective observational cross-sectional study. Within 1 year, each participant (n = 30) completed pulmonary function testing, echocardiogram, ECG, chest CT, AP spine radiography, and quality-of-life assessments (SF-36, St. George's Respiratory Questionnaire, Functional Outcomes of Sleep Questionnaire, and Pittsburgh Sleep Quality Index). In terms of pulmonary function, we differentiated restrictive and obstructive physiology using the ratio of forced expiratory volume over one second to forced vital capacity (FEV1/FVC), with restrictive lung physiology defined as FEV1/FVC > 0.8 and obstructive lung physiology as FEV1/FVC < 0.7. Spine radiographs were evaluated for scoliosis. Chest CT images were reviewed to qualitatively assess the lungs. The statistical analysis involved a Kruskall-Wallis test with Bonferroni's correction and a bivariate correlation analysis using Spearman's rho correlation coefficient (p < 0.05). Sixteen of 23 participants with restrictive lung physiology had scoliosis; their ages ranged from 19 years to 67 years. There was no correlation between the magnitude of the scoliosis curve and deficient pulmonary function (R = 0.08; p = 0.68). Seven participants had normal pulmonary function. The average scoliosis curve was 44 ± 29°. Thirteen participants had abnormal ECG findings while 10 had abnormal echocardiogram results. All but two individuals with abnormal chest CT results were found to have bronchial wall thickening. There were no differences in pulmonary or cardiac findings between OI types, except for FVC and total lung capacity, which were lower in individuals with Type III OI than in those with other types of OI. FEV1/FVC correlated with St. George's Respiratory Questionnaire (R = 0.429; p = 0.02) but not with Functional Outcomes of Sleep Questionnaire (R = -0.26; p = 0.19) or SF-36 scores (physical component summary: R = -0.037, p = 0.85; mental component summary: R = -0.204, p = 0.29). The lack of a relationship between decreased pulmonary function and the severity of scoliosis suggests that restrictive lung physiology in this population is likely because of factors intrinsic to OI and not entirely because of thoracic cage deformities. The fact that pulmonary impairment influences self-perceived quality of life exemplifies how detrimental such complications may be to everyday functioning. This also reinforces the importance of determining the underlying cause of cardiopulmonary impairment in this population to set clear clinical guidelines of care. Level II, prognostic study.

Target Workload For Exercise Challenge Tests Exceeds Achievable Workload In Children With Mild Asthma

PURPOSE: Exercise challenge tests are bronchoprovocation tests used to diagnose exercise induced bronchoconstriction. The American Thoracic Society (ATS) recommends calculating the target workload for exercise challenge tests using predicted forced expiratory volume in 1s (FEV1). The goal is for patients to achieve a minute ventilation between 40 to 60% of predicted maximum voluntary ventilation (PMVV) during the exercise challenge test. The purpose of this study was to compare predicted workload with actual workload achieved during an exercise challenge test in 8 to 12-year-old children with mild asthma. METHODS: Eleven children (3 girls, 10.3 ± 0.9 yr, 142.6 ± 8.1 cm, 40.7 ± 9.6 kg) completed pulmonary function testing and also completed maximal exercise tests and exercise challenge tests on a stationary bike. PMVV was calculated as 35 x measured FEV1. The test was completed at a target workload calculated using measured FEV1 (53.76 x measured FEV1 - 11.07). Our goal was to increase workload every minute as follows: 60%, 75%, 90%, and 100% target. However, if the child was unable to maintain cadence or expressed inability to complete 6 minutes of cycling, the workload was maintained or reduced to an achievable workload. RESULTS: 27% of children were below 40% PMVV, 36% were between 40 - 60% of PMVV, and 36% exceeded 60% of PMVV during the fifth minute of the exercise challenge test. After excluding the 3 children who did not achieve minute ventilation of at least 40% of PMVV, measured workload during the exercise challenge test (64 ± 18W; 66 ± 9%, Range: 49 - 78% of predicted target workload) was significantly lower than predicted target workload (96 ± 18W; P<0.001). Workload during the exercise challenge test was 67 ± 8% (Range: 60 - 80%) of maximum workload from the maximal exercise test. In the current project, we used measured FEV1 to calculate target workload for exercise challenge tests. However, even when predicted FEV1 was used to calculate target workload, measured workload during the exercise challenge test was below target and ranged from 43 - 112% (66 ± 22%) of target workload. CONCLUSIONS: The predicted workload for exercise challenge tests based on ATS guidelines may be difficult to achieve for children with mild asthma. However, target ventilation can be achieved at a workload that is between 60 - 80% of maximum workload.

Human Metapneumovirus Infections in Lung Transplant Recipients: The Effects on Lung Allograft and Clinical Outcomes

Human metapneumovirus infection (HMPVi) is a common community acquired infection in lung transplant recipients (LTRs), but data is very limited. This retrospective study of HMPVi in LTRs at the Johns Hopkins Hospital from Jan 2010 - April 2019 examined mortality, acute cellular rejection (ACR), donor specific antibody (DSA), chronic allograft dysfunction (CLAD) progression at 1 year after HMPVi as well as readmission, secondary bacterial/fungal infection at 90 days after HMPVi. The center's viral treatment practice included education for prompt diagnosis and consideration of ribavirin (RBV) usually with intravenous immunoglobulin (IVIG) for HMPVi. Of 31 HMPV infected LTRs, 22 received RBV (13 oral and 9 inhaled ribavirin) and 9 received supportive care only (SC). Baseline characteristics and infection parameters were similar among the 2 groups except concomitant respiratory bacterial pathogens at diagnosis, use of IVIG, and persistent HMPV shedding. In patients, whose respiratory viral PCR was repeated during day7-day30 post HMPVi, the SC group had significantly higher persistent viral shedding (66.7% vs 9.1% (RBV), p=0.03). There were no significant differences in readmission, death, CLAD progression, and DSA development among the 2 groups. The SC group had higher ACR rate (25% vs 0% (RBV), p = 0.03). Of 27 patients with complete pulmonary function tests, 11 (40.7%) developed CLAD progression within 1 year [50% (SC) vs 36.9% (RBV), p=0.53]. The SC group tended to have more fungal pathogen in respiratory samples (44.4% vs 13.6% (RBV), p= 0.06), but there were no significant differences in invasive fungal or bacterial infection at 90 days post HMPVs. Three patients reported side effects from RBV (nausea, diarrhea, and headache); none prematurely stopped RBV. RBV and IVIG may reduce risk of ACR and may help clear viral shedding. CLAD progression post HMPVi was 40% in this cohort and CLAD progression rates were not different among the 2 groups.

Pulmonary Imaging Phenotypes of Chronic Obstructive Pulmonary Disease Using Multiparametric Response Maps.

Background Pulmonary imaging of chronic obstructive pulmonary disease (COPD) has focused on CT or MRI measurements, but these have not been evaluated in combination. Purpose To generate multiparametric response map (mPRM) measurements in ex-smokers with or without COPD by using volume-matched CT and hyperpolarized helium 3 (3He) MRI. Materials and Methods In this prospective study (https://clinicaltrials.gov, NCT02279329), participants underwent MRI and CT and completed pulmonary function tests, questionnaires, and the 6-minute walk test between December 2010 and January 2019. Disease status was determined by using Global initiative for chronic Obstructive Lung Disease (GOLD) criteria. The mPRM voxel values were generated by using co-registered MRI and CT labels. Kruskal-Wallis and Bonferroni tests were used to determine differences across disease severity, and correlations were determined by using Spearman coefficients. Results A total of 175 ex-smokers (mean age, 69 years ± 9 [standard deviation], 108 men) with or without COPD were evaluated. Ex-smokers without COPD had a larger fraction of normal mPRM voxels (60% vs 37%, 20%, and 7% for GOLD I, II, and III/IV disease, respectively; all P ≤ .001) and a smaller fraction of abnormal voxels, including small airways disease (normal CT, not ventilated: 5% vs 6% [not significant], 11%, and 19% [P ≤ .001 for both] for GOLD I, II, and III/IV disease, respectively) and mild emphysema (normal CT, abnormal apparent diffusion coefficient [ADC]: 33% vs 54%, 56%, and 54% for GOLD I, II, and III/IV disease respectively; all P ≤ .001). Normal mPRM measurements were positively correlated with forced expiratory volume in 1 second (FEV1) (r = 0.65, P < .001), the FEV1-to-forced vital capacity ratio (r = 0.81, P < .001), and diffusing capacity (r = 0.75, P < .001) and were negatively correlated with worse quality of life (r = -0.48, P < .001). Abnormal mPRM measurements of small airways disease (normal CT, not ventilated) and mild emphysema (normal CT, abnormal ADC) were negatively correlated with FEV1 (r = -0.65 and -0.42, respectively; P < .001) and diffusing capacity (r = -0.53 and -0.60, respectively; P < .001) and were positively correlated with worse quality of life (r = 0.45 and r = 0.33, respectively; P < .001), both of which were present in ex-smokers without COPD. Conclusion Multiparametric response maps revealed two abnormal structure-function results related to emphysema and small airways disease, both of which were unexpectedly present in ex-smokers with normal spirometry and CT findings. © RSNA, 2020 Online supplemental material is available for this article.

Resting respiratory lung volumes are "healthier" than exercise respiratory volumes in different types of palliated or corrected congenital heart disease.

Cardiac surgery has improved life expectancy of patients with congenital heart diseases (CHDs). Exercise capacity is an important determinant of survival in patients with CHDs. There is a lack of studies focusing on the role of resting respiratory performance in reducing exercise tolerance in these patients. To determine the prevalence and severity of respiratory functional impairment in different types of corrected/palliated CHDs, and its impact on an exercise test. Retrospective single-center study involving 168 corrected/palliated patients with CHD and 52 controls. Patients CHD were divided into subgroups according to the presence of native pulmonary blood flow or total cavopulmonary connection (TCPC). All subjects performed complete pulmonary function tests and gas diffusion; patients with CHD also performed cardiopulmonary exercise test (CPX). Mean values of lung volumes were within the normal range in all CHD groups. Comparing to controls, patients with the reduced pulmonary flow and with TCPC had the highest reduction in lung volumes. CPX was reduced in all groups, most severely in TCPC, and it was correlated to decreased dynamic volumes in all CHD groups except in TCPC. Younger age at intervention and number of surgical operations negatively affected lung volumes. Respiratory function is within the normal range in our patients with different CHDs at rest but altered in all CHDs during exercise when cardiorespiratory balance is likely to be inadequate. Comparing the different groups, patients with reduced pulmonary flow and TCPC are the most impaired.

Relationship between pulmonary function and brachial-ankle pulse wave velocity in coal miners in northern China.

To investigate the relationship between pulmonary function and brachial-ankle pulse wave velocity (baPWV). A cross-sectional study was conducted. A total of 11,388 people with complete pulmonary function test and baPWV data and who participated in both the health examination of the Kailuan Occupational Disease Prevention and Treatment Center in 2014-2016 and the health checkup of the Kailuan Group in 2012 and 2014 were selected as subjects. The study population was divided into four groups by forced vital capacity (FVC) quartiles (group 1: FVC <3.50 L; group 2: 3.50 L ≤ FVC <3.96 L; group 3: 3.96 L ≤ FVC <4.47 L; group 4: FVC ≥4.47 L) and divided into four groups by forced expiratory volume in one second (FEV1) quartile (group 1: FEV1 <3.15 L; group 2: 3.15 L ≤ FVC <3.61 L; group 3: 3.61 L ≤ FVC <4.08 L; group 4: FVC ≥4.08 L). Linear regression analysis and multivariate logistic regression were used to analyze the effects of pulmonary function on baPWV. When grouped by FVC, the baPWV of the first group was significantly higher than the other groups. Similarly, the incidence of arteriosclerosis in the first group was significantly higher than the other groups. When grouped by FEV1, the baPWV of the first group was significantly higher than the other groups. The incidence of arteriosclerosis was also significantly higher in the first group than the other groups. After correcting for other confounding factors using linear regression, it was found that the effects of FVC and FEV1 on the study subject's baPWV were -23.84 and -24.65 L, respectively. Multivariate logistic regression analysis showed that when grouped by FVC quartile, the risk of arteriosclerosis was increased by 34% in group 1 compared with group 4 (OR: 1.34, 95% CI: 1.17-1.52); the risk of arteriosclerosis was increased by 16% in group 2 compared with group 4 (OR: 1.16, 95% CI: 1.03-1.31). When grouped by the FEV1 quartile, the risk of arteriosclerosis was increased by 25% in group 1 compared with group 4 (OR: 1.25, 95% CI: 1.10-1.42). Decreased pulmonary function is negatively correlated with baPWV and is an independent risk factor for arteriosclerosis.

Is a 12-h Nitrox dive hazardous for pulmonary function?

Prolonged exposure to a high partial pressure of oxygen leads to inflammation of pulmonary tissue [pulmonary oxygen toxicity (POT)], which is associated with tracheobronchial irritation, retrosternal pain and coughing, and decreases in vital capacity (VC). The nitric oxide (NO) concentration in exhaled gas (FeNO) has been used as an indicator of POT, but the effect of SCUBA diving on FeNO has rarely been studied. The study presented here aimed to assess alterations to pulmonary function and FeNO following a 12-h dive using breathing apparatus with a relatively high partial pressure of oxygen. Six healthy, male, non-smoking military SCUBA divers were recruited (age 31.8 ± 2.7years, height 179 ± 0.09cm, and body weight 84.6 ± 14kg). Each diver completed a 12-h dive using a demand-controlled semi-closed-circuit rebreather. During the 12h of immersion, divers were subjected to 672 oxygen toxicity units (OTU). A complete pulmonary function test (PFT) was completed the day before and immediately after immersion. FeNO was measured using a Nobreath™ Quark (COSMED™, Rome, Italy), three times for each diver. The first datapoint was collected before the dive to establish the "basal state", a second was collected immediately after divers emerged from the water, and the final measurement was taken 24h after the dive. Despite prolonged inhalation of a hyperoxic hyperbaric gas mixture, no clinical pulmonary symptoms were observed, and no major changes in pulmonary function were detected. However, a major decrease in FeNO values was observed immediately after emersion [0-12ppb (median, 3.8ppb)], with a return to baseline [2-60ppb (median, 26ppb) 24h later (3-73ppb (median, 24.7ppb)]. These results suggest that if the OTU remain below the recommended limit values, but does alter FeNO, this type of dive does not persistently impair lung function.

Prevalence and Factors Contributing to Daytime and Nocturnal Hypoxemia in Chronic Heart Failure Patients

Background: Despite clinical optimization, many chronic heart failure (CHF) patients remain symptomatic with dyspnea and poor quality of life. Study Objective: While oxygen therapy is prescribed in severe cases, the actual prevalence of different patterns of hypoxemia is unknown. Methods: We analyzed 183 stable CHF patients with optimized medical treatment in the “MARS” database. The patients underwent cardiorespiratory sleep recording and complete daytime pulmonary function tests including arterial blood gases. Results: This prospective cohort was predominately male (86.3%) with a mean age of 67.3 years (59.3; 75.7) and a mean BMI of 26.7 kg/m² (23.7; 31.1). The patients were mainly in NYHA classes II and III with a mean left ventricular ejection fraction of 38%. 102 (55.61%) patients had ischemic cardiomyopathy with multiple comorbidities, and 64 (35.06%) had airflow obstruction. 8 (4.37%) patients had hypoxemia both day and night, and 151 (82.5%) had nocturnal hypoxemia only. All but 3 patients had sleep-disordered breathing (SDB), and either obstructive (59%) or central sleep apnea (39%) with a mean apnea-hypopnea index of 29.59/h (16.48; 48.27), an oxygen desaturation index of 27.09/h (14.09; 45.25), time below 90% saturation of 18 min (2; 64), and a mean nocturnal saturation of 93% (92; 94). Univariate analysis found nocturnal hypoxemia was associated with higher BMI and NT-proBNP levels. In multivariate analysis, only sleep apnea severity (p < 0.0001) and diurnal PaO₂ remained significant. Conclusion: Most stable CHF patients suffer from nocturnal hypoxemia, while daytime hypoxemia is relatively rare. The degree of nocturnal hypoxemia depends on the severity of SDB. Hypoxemia phenotyping and severity could help better evaluate the need for appropriate therapy in CHF patients.

Forced oscillation technique in veterans with preserved spirometry and chronic respiratory symptoms

PurposeTo evaluate the utility of the forced oscillation technique (FOT) among military veterans with preserved spirometry and chronic unexplained respiratory symptoms. Methods178 veterans referred for evaluation of unexplained respiratory symptoms completed pulmonary function testing and FOT. Preserved spirometry was defined as FEV1/FVC, FEV1 and FVC ≥ 5th percentile. Frequency dependence of resistance (R4-R20) and reactance area (AX) were assessed via FOT, and R4-R20 ≥ 20% and AX ≥ 95th percentile were considered abnormal. ResultsSpirometry was preserved in 71.3%, of whom 124 had acceptable FOT data. 93 of 124 (75.0%) veterans with preserved spirometry had one or more abnormal findings on FOT. Veterans with abnormal R4-R20 and/or AX had reduced FVC, FEV1, FEF25-75, and diffusing capacity (% predicted) in comparison to those with Normal FOT (p = 0.030 to p < 0.001). ConclusionsIn our referral sample, distal airway dysfunction in the presence of preserved spirometry appears common and may represent an at-risk group requiring closer surveillance.

Pilot Results from an Integrated Pediatric Pulmonary Clinic on Outcomes in Children with Sickle Cell Disease

Abstract Introduction In children with sickle cell disease (SCD), asthma is a common comorbidity and is associated with increased disease severity when compared to children with SCD without asthma. Other pulmonary conditions, such as obstructive sleep apnea (OSA), are also more common in SCD and adversely affect clinical outcomes. Despite the well-established burden of pulmonary disease in children with SCD, optimal treatment paradigms are not well defined. Methods An integrated pediatric SCD and pulmonary clinic guided by the chronic care model was implemented at the University of Florida in July 2017 with the goal of coordinating subspecialty care and improving the treatment of concomitant pulmonary conditions. Prior to the formation of this clinic (pre-intervention phase), patients were managed separately by pulmonologists and hematologists in a tertiary academic medical center. During the intervention phase, patients received care in an interdisciplinary clinic composed of a pediatric pulmonologist, a pediatric hematologist with expertise in SCD, a respiratory therapist with access to an onsite pulmonary function testing (PFT) laboratory, asthma educator, and a SCD nurse educator/clinic coordinator. The objective of this abstract is to evaluate preliminary clinical outcomes of the integrated SCD-pulmonary clinic during the intervention phase (July 2017-June 2018) compared to 24 months prior to implementation (July 2015-June 2017). We hypothesized an integrated clinic model would improve access to specialized pulmonary care for children with SCD and reduce hospitalizations for vaso-occlusive episodes (VOEs). The primary endpoints are adherence to pulmonary clinic appointments and unplanned acute healthcare utilization for SCD-related complications and/or asthma exacerbations. Secondary endpoints are the number of unplanned packed red blood cell (PRBC) transfusions, percentage of patients able to complete PFTs, and new diagnoses or prescribed treatments during the intervention phase. Results During the intervention phase, 24 unique patients accounted for 40 clinic visits. Reasons for referral to the integrated SCD-pulmonary clinic included asthma (16), a history of severe and/or recurrent acute chest syndrome (12), OSA (3), hypoxia (1), shortness of breath (1), and concern for pulmonary hypertension (1). The mean age of participants was 10 years (range 2-18 years); 79% were male, 22 had hemoglobin (Hb) SS disease, 16 (67%) were being treated with hydroxyurea, and 2 were on chronic transfusion therapy. Mean baseline Hb and reticulocyte count were 9.1 gm/dL (SD 1.2) and 8.5% (SD 4.5), respectively. PFTs were successfully completed in 21 (88%) patients and reported as pre-treatment percent predicted values after adjusting for age, gender, height, and race. Mean forced expiratory volume in 1 second (FEV1) was 90% (SD 12.5), forced vital capacity (FVC) 94% (SD 12), and diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for Hb was 103% (SD 26, measured in 12 patients). Mean duration of follow-up was 8 months (range 1-12 months). During the pre-intervention phase, this cohort accounted for 76 hospitalizations, 42 emergency department (ED) visits, 31 transfusions, and 26 missed pulmonary appointments. During the intervention phase, there were 9 hospitalizations, 7 ED visits, 3 transfusions, and 5 missed appointments. This represents an 86% reduction in unplanned acute healthcare utilization (mean difference (MD) 2.8, 95% CI 1.8-3.7; p&lt;0.0001), a 90% reduction in PRBC transfusions (MD 1.9, 95% CI 0.96-2.78; p&lt;0.001), and an 81% increase in adherence to pulmonary appointments (MD 1.3, 95% CI 0.71-1.92; p&lt;0.001). Twenty-two patients had a confirmed asthma diagnosis, and 8 were diagnosed with OSA. Interventions included personalized asthma action plans (22 patients), inhaled corticosteroids (16), supplemental oxygen during sleep (5), tonsillectomy and adenoidectomy (2), and the initiation of hydroxyurea (1). Conclusions These results demonstrate that interdisciplinary clinics can improve access to subspecialty pulmonary care for children with SCD and support the continued development and implementation of integrated care models. With limited follow-up, the results also suggest integrated SCD and pulmonary care can reduce hospitalizations and ED visits for VOEs, though additional follow-up is required to determine the true treatment effect. Disclosures Black: Bioverativ: Membership on an entity's Board of Directors or advisory committees; NIH: Research Funding; Pfizer: Research Funding; Sancilio Pharmaceuticals: Research Funding; Prolong Pharmaceuticals: Consultancy.