"Horses for courses" computed tomography or predicted total lung capacity for size matching in lung transplantation.

Size-matching donors to recipients in lung transplantation continues to be a clinical challenge. Predicted total lung capacity equations, or more simply, donor and recipient heights, while widely used, are imprecise and may not be representative of the pool of donors and recipients. These inherent limitations may result in size discrepancies. The advent of easily accessible software and the widespread availability of computed tomography (CT) imaging in donor assessments have made it possible to directly measure lung volumes in donors and recipients. As a result, there is a growing interest in adopting personalized CT volumetry as an alternative. This article explores both methods and underscores the potential benefits and precision offered by CT.

Updated reference values for static lung volumes from a healthy population in Austria.

BACKGROUND: Reference values for lung volumes are necessary to identify and diagnose restrictive lung diseases and hyperinflation, but the values have to be validated in the relevant population. Our aim was to investigate the Global Lung Function Initiative (GLI) reference equations in a representative healthy Austrian population and create population-derived reference equations if poor fit was observed. METHODS: We analysed spirometry and body plethysmography data from 5371 respiratory healthy subjects (6-80 years) from the Austrian LEAD Study. Fit with the GLI equations was examined using z-scores and distributions within the limits of normality. LEAD reference equations were then created using the LMS method and the generalized additive model of location shape and scale package according to GLI models. RESULTS: Good fit, defined as mean z-scores between + 0.5 and -0.5,was not observed for the GLI static lung volume equations, with mean z-scores > 0.5 for residual volume (RV), RV/TLC (total lung capacity) and TLC in both sexes, and for expiratory reserve volume (ERV) and inspiratory capacity in females. Distribution within the limits of normality were shifted to the upper limit except for ERV. Population-derived reference equations from the LEAD cohort showed superior fit for lung volumes and provided reproducible results. CONCLUSION: GLI lung volume reference equations demonstrated a poor fit for our cohort, especially in females. Therefore a new set of Austrian reference equations for static lung volumes was developed, that can be applied to both children and adults (6-80 years of age).

Lung Volumes in a Mouse Model of Pulmonary Allergic Inflammation.

PURPOSE: Air trapping, often attested in humans by elevated residual volume (RV) and ratio of RV on total lung capacity (RV/TLC), is frequently observed in asthma. Confirming these alterations in experimental asthma would be important for translational purposes. Herein, lung volumes were investigated in a mouse model of pulmonary allergic inflammation. METHODS: Eight- to 10-week-old male C57BL/6 and BALB/c mice were exposed once daily to intranasal house dust mite (HDM) for 10 consecutive days. All readouts were measured 24 h after the last exposure. Lung volumes were assessed with the flexiVent using a new automated method consisting of degassing the lungs followed by a full-range pressure-volume maneuver. The weight and the volume of the lungs were also measured ex vivo and a lobe was further processed for histological analyses. RESULTS: HDM exposure led to tissue infiltration with inflammatory cells, goblet cell hyperplasia, thickening of the airway epithelium, and elevated ex vivo lung weight and volume. It also decreased TLC and vital capacity but without affecting RV and RV/TLC. These observations were similar between the two mouse strains. CONCLUSION: Alterations of lung volumes in a murine model of pulmonary allergic inflammation are inconsistent with observations made in human asthma. These discrepancies reflect the different means whereby lung volumes are measured between species. The invasive method used herein enables RV to be measured more precisely and without the confounding effect of air trapping, suggesting that changes in RV and RV/TLC using this method in mice should be interpreted differently than in humans.

The total-breath method yields higher values of DLCO and TLC than the conventional method.

BACKGROUND: The 2017 ATS/ERS technical standard for measuring the single-breath diffusing capacity (DLCO) proposed the "rapid-gas-analyzer" (RGA) or, equivalently, "total-breath" (TB) method for the determination of total lung capacity (TLC). In this study, we compared DLCO and TLC values estimated using the TB and conventional method, and how estimated TLC using these two methods compared to that determined by body plethysmography. METHOD: A total of 95 people with COPD (GOLD grades 1-4) and 23 healthy subjects were studied using the EasyOne Pro (ndd Medical Technologies, Switzerland) and Master Screen Body (Vyaire Medical, Höchberg, Germany). RESULTS: On average the TB method resulted in higher values of DLCO (mean ± SD Δ = 0.469 ± 0.267; 95%CI: 0.420; 0.517 mmol*min-1*kPa-1) and TLC (Δ = 0.495 ± 0.371; 95%CI: 0.427; 0.562 L) compared with the conventional method. In healthy subjects the ratio between TB and conventional DLCO was close to one. TLC estimated using both methods was lower than that determined by plethysmography. The difference was smaller for the TB method (Δ = 1.064 ± 0.740; 95%CI: 0.929; 1.199 L) compared with the conventional method (Δ = 1.558 ± 0.940; 95%CI: 1.387; 1.739 L). TLC from body plethysmography could be estimated as a function of TB TLC and FEV1 Z-Score with an accuracy (normalized root mean square difference) of 9.1%. CONCLUSION: The total-breath method yielded higher values of DLCO and TLC than the conventional analysis, especially in subjects with COPD. TLC from the total-breath method can also be used to estimate plethysmographic TLC with better accuracy than the conventional method. The study is registered under clinicaltrial.gov NCT04531293.

Do middle-aged patients with onset of idiopathic scoliosis before the age of 10 years who have reduced pulmonary function have a risk for rapid decline - a comparative study.

BACK GROUND: Knowledge concerning pulmonary function in adult patients with onset of idiopathic scoliosis before age 10 is sparse. A long-term follow-up (FU, mean 26 years, > 12 years after treatment) of pulmonary function (PF) in patients treated with brace or surgery due to idiopathic scoliosis with onset before the age of 10 was earlier performed. To evaluate whether a more severe reduction in pulmonary function leads to more rapid deterioration within a four-year period, this study was performed. METHODS: Twenty patients with the most reduced pulmonary function and 19 out of those with normal PF found at the long-term FU were reexamined 4 years later to evaluate further changes in pulmonary function. Patients underwent spirometry and arterial blood gas analysis and answered pulmonary symptom questionnaires. RESULTS: 70% of the reduced pulmonary function group had undergone surgery vs. 26% of the normal group. The mean age (47 vs. 43 years) at this FU and curve size (37° vs. 35°) at the 26-year FU were similar. The decline in forced vital capacity (FVC) % of predicted was similar in both groups over the four-year period, from 67 to 65% in the reduced PF group vs. 96 to 94% in the normal PF group. The total lung capacity (TLC) % of predicted did not change over time in either group. No patient reported worsening dyspnea symptoms. Only one patient in the reduced PF group showed low arterial oxygen tension, 8.4 kPa, not signifying respiratory insufficiency. CONCLUSION: The age-related decline in FVC and TLC % of predicted did not differ between those with reduced and those with normal pulmonary function at the 26-year follow-up. Thus, these data do not infer increased rate of decline in the most deteriorated patients.

Comprehensive appraisal of lung function in young COPD patients: a single center observational study.

PURPOSE: The present study aimed to investigate the clinical characteristics and lung function impairment in young people diagnosed with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: We retrospectively enrolled patients with COPD who underwent symptom assessment and comprehensive pulmonary function tests at the First Affiliated Hospital of Guangzhou Medical University between August 2017 and March 2022. The patients were categorized into two groups based on age: a young COPD group (aged 20-50 years) and an old COPD group (aged > 50 years). RESULTS: A total of 1282 patients with COPD were included in the study, with 76 young COPD patients and 1206 old COPD patients. Young COPD patients exhibited a higher likelihood of being asymptomatic, lower rates of smoking, and a lower smoking index compared to old COPD patients. Although young COPD patients had higher median post-bronchodilator forced expiratory volume in 1 s (post-BD FEV1) (1.4 vs.1.2 L, P = 0.019), diffusing capacity of the lung for carbon monoxide (DLCO) (7.2 vs. 4.6, P<0.001), and a lower median residual volume to total lung capacity ratio (RV/TLC) compared to their older counterparts, there were no differences observed in severity distribution by GOLD categories or the proportion of lung hyperinflation (RV/TLC%pred > 120%) between two groups. Surprisingly, the prevalence of reduced DLCO was found to be 71.1% in young COPD, although lower than in old COPD (85.2%). CONCLUSION: Young COPD showed fewer respiratory symptoms, yet displayed a similar severity distribution by GOLD categories. Furthermore, a majority of them demonstrated lung hyperinflation and reduced DLCO. These results underscore the importance of a comprehensive assessment of lung function in young COPD patients.

Hypercapnia and lung function parameters in chronic obstructive pulmonary disease.

BACKGROUND: In advanced chronic obstructive pulmonary disease (COPD), hypercapnia may occur due to severe bronchial obstruction with lung hyperinflation. Non-invasive ventilation (NIV) provides the standard of care intended to achieve physiological PCO2 levels, thereby reducing overall mortality. The present study aimed to evaluate pulmonary function parameters derived from spirometry (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1]), body plethysmography (residual volume [RV], total lung capacity [TLC]), and lung diffusion capacity for carbon monoxide (single-breath method [DCO-SB], alveolar-volume corrected values [DCO-VA]) as predictors of chronic hypercapnia in patients with advanced COPD. METHODS: This monocentric, retrospective observational study included 423 COPD patients. Receiver operating characteristic (ROC) curve analysis and cross-validation were used to assess lung function parameters' diagnostic accuracy for predicting chronic hypercapnia, with the resulting performance expressed as area under the ROC curve (AUROC). We performed univariable and multivariable binary logistic regression analysis to determine if these parameters were independently associated with chronic hypercapnia, with probabilities reported as odds ratios [OR] with 95% confidence intervals [95%CI]. RESULTS: FVC% (AUROC 0.77 [95%CI 0.72-0.81], P < 0.01) and FEV1% (AURIC 0.75 [95%CI 0.70-0.79], P < 0.01) exhibited reasonable accuracy in the prediction of chronic hypercapnia, whereas lung diffusion capacity performed poorly (AUROC 0.64 [95%CI 0.58-0.71] for DCO-SB%, P < 0.01). FVC% (OR 0.95 [95%CI 0.93-0.97], P < 0.01) and FEV1% (OR 0.97 [95%CI 0.94-0.99], P = 0.029) were the only parameters associated independently with chronic hypercapnia in logistic regression analysis. FVC and FEV1 thresholds that best separated hypercapnic from normocapnic subjects reached 56% and 33% of predicted values. CONCLUSIONS: Routinely collected pulmonary function parameters, particularly FVC% and FEV1%, may predict chronic hypercapnia during COPD progression.

Quantitative CT analysis of idiopathic pulmonary fibrosis and correlation with lung function study.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a progressive fibrotic lung disease. However, the field of quantitative CT scan analysis in conjunction with pulmonary function test for IPF patients remains relatively understudied. In this study, we evaluated the diagnostic value of features derived high-resolution computed tomography (HRCT) for patients with IPF and correlated them with pulmonary function tests. METHODS: We retrospectively analyzed the chest HRCT images and pulmonary function test results of 52 patients with IPF during the same period (1 week) and selected 52 healthy individuals, matched for sex, age, and body mass index (BMI) and with normal chest HRCT as controls. HRCT scans were performed using a Philips 256-row Brilliance iCT scanner with standardized parameters. Lung function tests were performed using a Jaeger volumetric tracer for forced vital capacity (FVC), total lung capacity (TLC), forced expiratory volume in first second (FEV1), FEV1/FVC, carbon monoxide diffusing capacity (DLCO), and maximum ventilation volume (MVV) metrics. CT quantitative analysis, including tissue segmentation and threshold-based quantification of lung abnormalities, was performed using 3D-Slicer software to calculate the percentage of normal lung areas (NL%), percentage of ground-glass opacity areas (GGO%), percentage of fibrotic area (F%) and abnormal lesion area percentage (AA%). Semi-quantitative analyses were performed by two experienced radiologists to assess disease progression. The aortic-to-sternal distance (ASD) was measured on axial images as a standardized parameter. Spearman or Pearson correlation analysis and multivariate stepwise linear regression were used to analyze the relationship between the data in each group, and the ROC curve was used to determine the optimal quantitative CT metrics for identifying IPF and controls. RESULTS: ROC curve analysis showed that F% distinguished the IPF patient group from the control group with the largest area under the curve (AUC) of 0.962 (95% confidence interval: 0.85-0.96). Additionally, with F% = 4.05% as the threshold, the Youden's J statistic was 0.827, with a sensitivity of 92.3% and a specificity of 90.4%. The ASD was significantly lower in the late stage of progression than in the early stage (t = 5.691, P < 0.001), with a mean reduction of 2.45% per month. Quantitative CT indices correlated with all pulmonary function parameters except FEV1/FVC, with the highest correlation coefficients observed for F% and TLC%, FEV1%, FVC%, MVV% (r = - 0.571, - 0.520, - 0.521, - 0.555, respectively, all P-values < 0.001), and GGO% was significantly correlated with DLCO% (r = - 0.600, P < 0.001). Multiple stepwise linear regression analysis showed that F% was the best predictor of TLC%, FEV1%, FVC%, and MVV% (R2 = 0.301, 0.301, 0.300, and 0.302, respectively, all P-values < 0.001), and GGO% was the best predictor of DLCO% (R2 = 0.360, P < 0.001). CONCLUSIONS: Quantitative CT analysis can be used to diagnose IPF and assess lung function impairment. A decrease in the ASD may indicate disease progression.

Preserved ratio impaired spirometry is associated with small airway dysfunction and reduced total lung capacity.

BACKGROUND: Preserved ratio impaired spirometry (PRISm) refers to decreased forced expiratory volume in 1 s (FEV1) in the setting of preserved ratio. Little is known about the role of PRISm and its complex relation with small airway dysfunction (SAD) and lung volume. Therefore, we aimed to investigate the associations between PRISm and SAD and lung volume. METHODS: We conducted a cross-sectional community-dwelling study in China. Demographic data, standard respiratory epidemiology questionnaire, spirometry, impulse oscillometry (IOS) and computed tomography (CT) data were collected. PRISm was defined as post-bronchodilator FEV1/FVC ≥ 0.70 and FEV1 < 80% predicted. Spirometry-defined SAD was defined as at least two of three of the post-bronchodilator maximal mid-expiratory flow (MMEF), forced expiratory flow 50% (FEF50), and forced expiratory flow 75% (FEF75) less than 65% of predicted. IOS-defined SAD and CT-defined gas trapping were defined by the fact that the cutoff value of peripheral airway resistance R5-R20 > 0.07 kPa/L/s and LAA- 856>20%, respectively. Analysis of covariance and logistic regression were used to determine associations between PRISm and SAD and lung volume. We then repeated the analysis with a lower limit of normal definition of spirometry criteria and FVC definition of PRISm. Moreover, we also performed subgroup analyses in ever smoker, never smoker, subjects without airway reversibility or self-reported diagnosed asthma, and subjects with CT-measured total lung capacity ≥70% of predicted. RESULTS: The final analysis included 1439 subjects. PRISm had higher odds and more severity in spirometry-defined SAD (pre-bronchodilator: odds ratio [OR]: 5.99, 95% confidence interval [95%CI]: 3.87-9.27, P < 0.001; post-bronchodilator: OR: 14.05, 95%CI: 8.88-22.24, P < 0.001), IOS-defined SAD (OR: 2.89, 95%CI: 1.82-4.58, P < 0.001), and CT-air trapping (OR: 2.01, 95%CI: 1.08-3.72, P = 0.027) compared with healthy control after adjustment for confounding factors. CT-measured total lung capacity in PRISm was lower than that in healthy controls (4.15 ± 0.98 vs. 4.78 ± 1.05 L, P < 0.05), after adjustment. These results were robust in repeating analyses and subgroup analyses. CONCLUSION: Our finding revealed that PRISm was associated with SAD and reduced total lung capacity. Future studies to identify the underlying mechanisms and longitudinal progression of PRISm are warranted.

Influence of gender on diaphragm thickness using a method for determining intima media thickness in healthy young adults.

BACKGROUND: To clarify the differences in diaphragm thickness between male and female participants in healthy young adults with ultrasonography using the mean intima media thickness (IMT) method and to investigate the relationship between diaphragm thickness and respiratory pressure. METHODS: Twenty-nine healthy individuals (16 females and 13 males) participated in the study. Diaphragm thickness was measured at total lung capacity (TLC) and at functional residual capacity (FRC) in each participant. We measured the diaphragm thickness using a method for mean intima media thickness. Moreover, change ratio of diaphragm thickness was calculated with the diaphragm thickness at TLC and FRC. RESULTS: Mean diaphragm thicknesses at FRC in males were significantly narrower than those in females (p < 0.001). The change ratio of diaphragm thickness was significantly augmented in males compared with that in females (p < 0.001). There was a positive correlation between the change ratio of diaphragm thickness and pulmonary function data and respiratory muscle strength in healthy young adults. CONCLUSIONS: The change ratio of diaphragm thickness using the IMT method can be accurately performed with a high degree of reproducibility by clinical laboratory technicians and may be a useful indicator for evaluating diaphragm muscle strength.

Tidal volume expandability affected by flow, dynamic hyperinflation, and quasi-fixed inspiratory time in patients with COPD and healthy individuals.

Exertional dyspnea (ED) and impaired exercise performance (EP) are mainly caused by dynamic hyperinflation (DH) in chronic obstructive pulmonary disease (COPD) patients by constraining tidal volume expansion at peak exercise (VTpeak). As VTpeak is the product of inspiratory time (TIpeak) and flow (VT/TIpeak), it was hypothesized that VTpeak and VTpeak/total lung capacity (VTpeak/TLC) may be affected by TIpeak and VT/TIpeak. Hence, the study investigated the (1) effect of TIpeak and VT/TIpeak on VTpeak expansion, (2) factors associated with TIpeak, expiratory time (TEpeak), VT/TIpeak, and VTpeak/TLC, and (3) relationships between VT/TIpeak and VTpeak/TLC with ED and EP in COPD patients and controls. The study enrolled 126 male stable COPD patients and 33 sex-matched controls. At peak exercise, TIpeak was similar in all subjects (COPD versus controls, mean ± SD: 0.78 ± 0.17 s versus 0.81 ± 0.20 s, p = NS), whereas the COPD group had lower VT/TIpeak (1.71 ± 0.49 L/s versus 2.58 ± 0.69 L/s, p < .0001) and thus the COPD group had smaller VTpeak (1.31 ± 0.34 L versus 2.01 ± 0.45 L,p < .0001) and VTpeak/TLC (0.22 ± 0.06 vs 0.33 ± 0.05, p < .0001). TIpeak, TEpeak, and VT/TIpeak were mainly affected by exercise effort, whereas VTpeak/TLC was not. TEpeak, VT/TIpeak, and VTpeak/TLC were inversely changed by impaired lung function. TIpeak was not affected by lung function. Dynamic hyperinflation did not occur in the controls, however, VTpeak/TLC was strongly inversely related to DH (r = -0.79) and moderately to strongly related to lung function, ED, and EP in the COPD group. There was a slightly stronger correlation between VTpeak/TLC with ED and EP than VT/TIpeak in the COPD group (|r| = 0.55-0.56 vs 0.38-0.43). In summary, TIpeak was similar in both groups and the key to understanding how flow affects lung expansion. However, the DH volume effect was more important than the flow effect on ED and EP in the COPD group.

Official ERS technical standard: Global Lung Function Initiative reference values for static lung volumes in individuals of European ancestry.

BACKGROUND: Measurement of lung volumes across the life course is critical to the diagnosis and management of lung disease. The aim of the study was to use the Global Lung Function Initiative methodology to develop all-age multi-ethnic reference equations for lung volume indices determined using body plethysmography and gas dilution techniques. METHODS: Static lung volume data from body plethysmography and gas dilution techniques from individual, healthy participants were collated. Reference equations were derived using the LMS (lambda-mu-sigma) method and the generalised additive models of location shape and scale programme in R. The impact of measurement technique, equipment type and being overweight or obese on the derived lung volume reference ranges was assessed. RESULTS: Data from 17 centres were submitted and reference equations were derived from 7190 observations from participants of European ancestry between the ages of 5 and 80 years. Data from non-European ancestry populations were insufficient to develop multi-ethnic equations. Measurements of functional residual capacity (FRC) collected using plethysmography and dilution techniques showed physiologically insignificant differences and were combined. Sex-specific reference equations including height and age were developed for total lung capacity (TLC), FRC, residual volume (RV), inspiratory capacity, vital capacity, expiratory reserve volume and RV/TLC. The derived equations were similar to previously published equations for FRC and TLC, with closer agreement during childhood and adolescence than in adulthood. CONCLUSIONS: Global Lung Function Initiative reference equations for lung volumes provide a generalisable standard for reporting and interpretation of lung volumes measurements in individuals of European ancestry.

Interventional bronchoscopy for chronic obstructive pulmonary disease: more than a pipe dream.

Endoscopic lung volume reduction (ELVR) is recognised in both national and international expert guidelines as one of the few additive treatments to benefit patients with advanced chronic obstructive pulmonary disease (COPD) who are otherwise receiving optimal medical and supportive care. Despite these recommendations and a growing evidence base, these procedures are not widely offered across Australia and New Zealand, and general practitioner and physician awareness of this therapy can be improved. ELVR aims to mitigate the impact of hyperinflation and gas trapping on dyspnoea and exercise intolerance in COPD. Effective ELVR is of proven benefit in improving symptoms, quality of life, lung function and survival. Several endoscopic techniques to achieve ELVR have been developed, with endobronchial valve placement to collapse a single lobe being the most widely studied and commonly practised. This review describes the physiological rationale underpinning lung volume reduction, highlights the challenges of patient selection, and provides an overview of the evidence for current and investigational endoscopic interventions for COPD.

Ventilation Heterogeneity in Asthma and COPD: The Value of the Poorly Communicating Fraction as the Ratio of Total Lung Capacity to Alveolar Volume.

BACKGROUND: The ventilation heterogeneity (VH) is reliably assessed by the multiple-breath nitrogen washout (MBNW), which provides indices of conductive (Scond) and acinar (Sacin) VH as well as the lung clearance index (LCI), an index of global VH. VH can be alternatively measured by the poorly communicating fraction (PCF), that is, the ratio of total lung capacity by body plethysmography to alveolar volume from the single-breath lung diffusing capacity measurement. OBJECTIVES: Our objective was to assess VH by PCF and MBNW in patients with asthma and with COPD and to compare PCF and MBNW parameters in both patient groups. METHOD: We studied 35 asthmatic patients and 45 patients with COPD. Each patient performed spirometry, body plethysmography, diffusing capacity, and MBNW test. RESULTS: Compared to COPD patients, asthmatics showed a significantly lesser degree of airflow obstruction and lung hyperinflation. In asthmatic patients, both PCF and LCI and Sacin values were significantly lower than the corresponding ones of COPD patients. In addition, in both patient groups, PCF showed a positive correlation with LCI (p < 0.05) and Sacin (p < 0.05), but not with Scond. Lastly, COPD patients with PCF >30% were highly likely to have a value ≥2 of the mMRC dyspnea scale. CONCLUSIONS: These results showed that PCF, a readily measure derived from routine pulmonary function testing, can provide a comprehensive measure of both global and acinar VH in asthma and in COPD patients and can be considered as a comparable tool to the well-established MBNW technique.

Pneumothorax in Patients with Idiopathic Pleuroparenchymal Fibroelastosis: Incidence, Clinical Features, and Risk Factors.

BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare form of idiopathic interstitial pneumonia that is characterized by predominantly upper lobe pleural and subpleural lung parenchymal fibrosis. Pneumothorax is one of the major respiratory complications in PPFE patients; however, its clinical features are poorly understood. OBJECTIVE: We aimed to investigate the complication of pneumothorax in patients with idiopathic PPFE. METHODS: A retrospective multicenter study involving 89 patients who had been diagnosed with idiopathic PPFE was conducted. We investigated the cumulative incidence, clinical features, and risk factors of pneumothorax after the diagnosis of idiopathic PPFE. RESULTS: Pneumothorax developed in 53 patients (59.6%) with 120 events during the observation period (41.8 ± 35.0 months). The cumulative incidence of pneumothorax was 24.8, 44.9, and 53.9% at 1, 2, and 3 years, respectively. Most events of pneumothorax were asymptomatic (n = 85; 70.8%) and small in size (n = 92; 76.7%); 30 patients (56.6%) had recurrent pneumothorax. Chest drainage was required in 23 pneumothorax events (19.2%), and a persistent air leak was observed in 13 (56.5%). Patients with pneumothorax were predominantly male and frequently had pathological diagnoses of PPFE and prior history of pneumothorax and corticosteroid use; they also had significantly poorer survival than those without pneumothorax (log-rank test; p = 0.001). Multivariate analysis revealed that a higher residual volume/total lung capacity ratio was significantly associated with the development of pneumothorax after the diagnosis. CONCLUSION: Pneumothorax is often asymptomatic and recurrent in patients with idiopathic PPFE, leading to poor outcomes in some cases.

Development and Progression of Radiologic Abnormalities in Individuals at Risk for Familial Interstitial Lung Disease.

Rationale: The preclinical natural history of progressive lung fibrosis is poorly understood.Objectives: Our goals were to identify risk factors for interstitial lung abnormalities (ILA) on high-resolution computed tomography (HRCT) scans and to determine progression toward clinical interstitial lung disease (ILD) among subjects in a longitudinal cohort of self-reported unaffected first-degree relatives of patients with familial interstitial pneumonia.Methods: Enrollment evaluation included a health history and exposure questionnaire and HRCT scans, which were categorized by visual assessment as no ILA, early/mild ILA, or extensive ILA. The study endpoint was met when ILA were extensive or when ILD was diagnosed clinically. Among subjects with adequate study time to complete 5-year follow-up HRCT, the proportion with ILD events (endpoint met or radiographic ILA progression) was calculated.Measurements and Main Results: Among 336 subjects, the mean age was 53.1 (SD, 9.9) years. Those with ILA (early/mild [n = 74] or extensive [n = 3]) were older, were more likely to be ever smokers, had shorter peripheral blood mononuclear cell telomeres, and were more likely to carry the MUC5B risk allele. Self-reported occupational or environmental exposures, including aluminum smelting, lead, birds, and mold, were independently associated with ILA. Among 129 subjects with sufficient study time, 25 (19.4%) had an ILD event by 5 years after enrollment; of these, 12 met the study endpoint and another 13 had radiologic progression of ILA. ILD events were more common among those with early/mild ILA at enrollment (63.3% vs. 6.1%; P < 0.0001).Conclusions: Rare and common environmental exposures are independent risk factors for radiologic abnormalities. In 5 years, progression of ILA occurred in most individuals with early ILA detected at enrollment.

Roxadustat (FG-4592) accelerates pulmonary growth, development, and function in a compensatory lung growth model.

Children with hypoplastic lung disease associated with congenital diaphragmatic hernia (CDH) continue to suffer significant morbidity and mortality secondary to progressive pulmonary disease. Current management of CDH is primarily supportive and mortality rates of the most severely affected children have remained unchanged in the last few decades. Previous work in our lab has demonstrated the importance of vascular endothelial growth factor (VEGF)-mediated angiogenesis in accelerating compensatory lung growth. In this study, we evaluated the potential for Roxadustat (FG-4592), a prolyl hydroxylase inhibitor known to increase endogenous VEGF, in accelerating compensatory lung growth. Treatment with Roxadustat increased lung volume, total lung capacity, alveolarization, and exercise tolerance compared to controls following left pneumonectomy. However, this effect was likely modulated not only by increased VEGF, but rather also by decreased pigment epithelium-derived factor (PEDF), an anti-angiogenic factor. Furthermore, this mechanism of action may be specific to Roxadustat. Vadadustat (AKB-6548), a structurally similar prolyl hydroxylase inhibitor, did not demonstrate accelerated compensatory lung growth or decreased PEDF expression following left pneumonectomy. Given that Roxadustat is already in Phase III clinical studies for the treatment of chronic kidney disease-associated anemia with minimal side effects, its use for the treatment of pulmonary hypoplasia could potentially proceed expeditiously.

Quantitative CT-based structural alterations of segmental airways in cement dust-exposed subjects.

BACKGROUND: Dust exposure has been reported as a risk factor of pulmonary disease, leading to alterations of segmental airways and parenchymal lungs. This study aims to investigate alterations of quantitative computed tomography (QCT)-based airway structural and functional metrics due to cement-dust exposure. METHODS: To reduce confounding factors, subjects with normal spirometry without fibrosis, asthma and pneumonia histories were only selected, and a propensity score matching was applied to match age, sex, height, smoking status, and pack-years. Thus, from a larger data set (N = 609), only 41 cement dust-exposed subjects were compared with 164 non-cement dust-exposed subjects. QCT imaging metrics of airway hydraulic diameter (Dh), wall thickness (WT), and bifurcation angle (θ) were extracted at total lung capacity (TLC) and functional residual capacity (FRC), along with their deformation ratios between TLC and FRC. RESULTS: In TLC scan, dust-exposed subjects showed a decrease of Dh (airway narrowing) especially at lower-lobes (p < 0.05), an increase of WT (wall thickening) at all segmental airways (p < 0.05), and an alteration of θ at most of the central airways (p < 0.001) compared with non-dust-exposed subjects. Furthermore, dust-exposed subjects had smaller deformation ratios of WT at the segmental airways (p < 0.05) and θ at the right main bronchi and left main bronchi (p < 0.01), indicating airway stiffness. CONCLUSIONS: Dust-exposed subjects with normal spirometry demonstrated airway narrowing at lower-lobes, wall thickening at all segmental airways, a different bifurcation angle at central airways, and a loss of airway wall elasticity at lower-lobes. The airway structural alterations may indicate different airway pathophysiology due to cement dusts.

Chest CT imaging features for prediction of treatment response in cryptogenic and connective tissue disease-related organizing pneumonia.

OBJECTIVES: To investigate CT imaging features associated with poor clinical outcome after corticosteroid treatment in patients diagnosed with cryptogenic organizing pneumonia (COP) and connective tissue disease-related organizing pneumonia (CTD-OP) and to assess the difference in CT findings and treatment responses between COP and CTD-OP. METHODS: Chest CT images from 166 patients (COP, 131; CTD-OP, 35) with pathologically proven organizing pneumonia were reviewed by two thoracic radiologists. The type, distribution pattern, and extent of parenchymal abnormalities, along with other associated imaging features, were assessed for each patient. Logistic regression analyses were used to identify features associated with poor clinical outcomes such as residual disease (RD) and disease relapse. The differences between COP and CTD-OP were also analyzed. RESULTS: Consolidation involving more than 10% of parenchyma (hazard ratio [HR], 2.27), detectable bronchiectasis (HR, 3.59), and diagnosis of CTD-OP (HR, 4.31) were associated with a higher risk of RD after adjustments for patient age and sex. More than 10% consolidation involvement (HR, 2.54) and diagnosis of CTD-OP (HR, 6.42) were also associated with a higher risk of disease relapse. Compared with COP, CTD-OP demonstrated a greater extent of parenchymal abnormalities, especially consolidation, and was less likely to show a peribronchovascular distribution pattern. CONCLUSION: Bronchiectasis and a greater extent of consolidation were associated with RD, with the latter also being associated with disease relapse. Compared with COP, CTD-OP was associated with worse treatment outcomes and demonstrated a greater extent of parenchymal abnormalities, which were also less likely to show a peribronchovascular pattern. KEY POINTS: • The presence of bronchiectasis and a high parenchymal involvement of consolidation on initial chest CT were associated with a worse response to corticosteroids in patients with organizing pneumonia. • Connective tissue disease-related organizing pneumonia (CTD-OP) was associated with worse treatment outcomes than its idiopathic counterpart cryptogenic organizing pneumonia (COP). • Compared with COP, CTD-OP generally demonstrated a greater extent of parenchymal abnormalities, especially consolidation, and was less likely to show a peribronchovascular distribution pattern.

Impact of Azathioprine use in chronic hypersensitivity pneumonitis patients.

INTRODUCTION: Systemic corticosteroids are widely used in chronic hypersensitivity pneumonitis (CHP); however, there is not much evidence to support their use, besides being associated with significant side effects. Azathioprine (AZA) use is common in CHP, although not prospectively tested in randomized controlled trials. Our objective was to evaluate the lung function trajectory of CHP patients after AZA initiation, as well as to assess the safety profile of this drug. METHODS: Retrospective analysis of patients initiated on AZA following a multidisciplinary team diagnosis of CHP. The longitudinal trajectory of lung function in the first 2 years of treatment was assessed. RESULTS: Thirty-five out of 62 patients (56.5%) remained on treatment after 2 years. AZA treatment was associated with a significant improvement in forced vital capacity (FVC) at 12 and 24 months (p = 0.015 and p < 0.001, respectively). A slight increase in total lung capacity (TLC) and 6-min walking test (6MWT) were also reported, although it did not reach statistical differences at the end of 2 years. No changes in diffusion capacity for carbon monoxide (DLCO) were observed. CONCLUSIONS: This is the first study identifying an improvement in lung function (FVC) of CHP patients on AZA treatment for 2 years. Prospective studies are needed to confirm these results and to more adequately select CHP patients who may benefit from AZA.