Low DLCO Research Articles

Risk factors for progression of pulmonary fibrosis: a single-centered, retrospective study.

This study aimed to identify clinical characteristics associated with the prevalence of progressive pulmonary fibrosis (PPF) in interstitial lung disease (ILD) and to develop a prognostic nomogram model for clinical use. In this single-centered, retrospective study, we enrolled ILD patients with relatively comprehensive clinical data and assessed the incidence of PPF within a year using collected demographics, laboratory data, high-resolution computed tomography (HRCT), and pulmonary function test (PFT) results. We used a training cohort of ILD patients to identify early predictors of PPF and then validated them in an internal validation cohort and subsets of ILD patients using a multivariable logistic regression analysis. A prognostic nomogram was formulated based on these predictors, and the accuracy and efficiency were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis (DCA). Among the enrolled patients, 120 (39.09%) cases had connective tissue disease-associated interstitial lung disease (CTD-ILD), 115 (37.46%) had non-idiopathic pulmonary fibrosis idiopathic interstitial pneumonia (non-IPF IIP), and 35 (11.4%) had hypersensitivity pneumonitis (HP). Overall, 118 (38.4%) cases experienced pulmonary fibrosis progression. We found that baseline DLco% pred (OR 0.92; 95% CI, 8.93-0.95) was a protective factor for ILD progression, whereas combined pneumonia (OR 4.57; 95% CI, 1.24-18.43), modified Medical Research Council dyspnea score (mMRC) (OR 4.9; 95% CI, 2.8-9.5), and high-resolution computed tomography (HRCT) score (OR 1.22; 95% CI, 1.07-1.42) were independent risk factors for PPF. The AUC of the proposed nomogram in the development cohort was 0.96 (95% CI, 0.94, 0.98), and the calibration plot showed good agreement between the predicted and observed incidence of PPF (Hosmer-Lemeshow test: P = 0.86). ILD patients with combined pneumonia, low baseline DLco% pred, high mMRC marks, and high HRCT scores were at higher risk of progression. This nomogram demonstrated good discrimination and calibration, indicating its potential utility for clinical practice.

Frequency and characteristics of refractory dyspnea in idiopathic fibrosing interstitial pneumonia

Patients with idiopathic fibrosing interstitial pneumonias (f-IIPs) mainly suffer from dyspnea. Refractory dyspnea, defined as persistent dyspnea despite optimal treatment, could be the signal to prescribe dyspnea relievers. We aimed to examine the prevalence and characteristics of refractory dyspnea in consecutive patients with f-IIPs.Refractory dyspnea was defined by an mMRC≥3 and also by a VAS dyspnea score≥2 at rest. The sensory and affective characteristics of refractory dyspnea (mMRC≥3) and associated quality of life (QoL) anxiety and depression were compared with non-refractory dyspnea (mMRC1-2) using the Multidimensional Dyspnea Profile (MDP), King's Brief Interstitial Lung Disease (KBILD) and Hospital Anxiety and Depression scale (HADs).We included 40 patients (24 men), aged 72 [68–79], FVC of 71 % [59–86] and DLCO 47 % [40–49]. Refractory dyspnea, was found in 38 % (95%CI:23–54) when defined by mMRC≥3 and in 67 % (95%CI:50–81) using a resting VAS dyspnea score ≥2. The agreement between the two definitions was low. Patients with refractory dyspnea (mMRC≥3) were more often women (60 % vs.28 %, p = 0.046), had a lower DLCO (24 % [22–43] vs.47 % [43–51], p = 0.014) and more frequently used oxygen (60 % vs.12 %, p = 0.003); they experience more intense air hunger (5/10 [3-6] vs.2/10 [0–5], p = 0.018)). No significant differences were observed in VAS, MDP, KBILD, or HADs scores between refractory and non-refractory dyspnea patients.Our results indicate a significant frequency of refractory dyspnea in patients with f-IIPs and an association with air hunger but no impact on the affective dimension of dyspnea, anxiety, depression and QoL, suggesting that the mMRC score might not accurately identify patients distressed by their breathlessness.

Corticosteroid treatment for persistent pulmonary infiltrates following COVID-19 infection: Clearing the fog?

Systemic corticosteroids have been shown to improve outcomes in severe coronavirus disease 2019 (COVID-19) pneumonia; however, their role in post-COVID-19 persistent lung abnormalities is not well defined. Here, we describe our experience with corticosteroids in patients with persistent lung infiltrates following COVID-19 infection. What is the efficacy of systemic corticosteroids in improving lung function and radiological abnormalities in patients following COVID-19 pneumonia? This is a single-center retrospective study evaluating patients with persistent respiratory symptoms and abnormal chest computed tomography findings. Patients were divided into two groups based on treatment with corticosteroids: "steroid group" and "nonsteroid group." Clinical data were collected from the electronic medical records. Between March 2020 and December 2021, 227 patients were seen in the post-COVID-19 pulmonary clinic, of which 75 were included in this study. The mean age was 56 years, 63% were female, and 75% were white. The main physiologic deficit was reduced Diffusing capacity of the Lungs for Carbon Monoxide (DLCO) at 72% (±22). On chest imaging, the most common findings were ground-glass opacities (91%) and consolidation (29%). Thirty patients received corticosteroid (steroid group) and 45 did not (nonsteroid group). Patients treated with corticosteroids had lower DLCO (DLCO [%]: steroid group 63 ± 17, nonsteroid group 78 ± 23; P = 0.005) and all had ground-glass opacities on imaging compared to 84% in the nonsteroid group (P = 0.04). At follow-up, patients in the steroid group (n = 16) had a significant improvement in spirometry and DLCO. In addition, there was a significant improvement with resolution of ground-glass opacities in both the groups (P < 0.05). The use of systemic corticosteroids in patients with persistent respiratory symptoms and radiological abnormalities post-COVID-19 was associated with significant improvement in pulmonary function testing and imaging. Prospective studies are needed to confirm whether these findings are the effect of corticosteroid therapy or disease evolution over time.

Beyond the Acute Phase: Long-Term Impact of COVID-19 on Functional Capacity and Prothrombotic Risk-A Pilot Study.

Background and Objectives: Assessment of the prothrombotic, proinflammatory, and functional status of a cohort of COVID-19 patients at least two years after the acute infection to identify parameters with potential therapeutic and prognostic value. Materials and Methods: We conducted a retrospective, descriptive study that included 117 consecutive patients admitted to Iasi Pulmonary Rehabilitation Clinic for reassessment and a rehabilitation program at least two years after a COVID-19 infection. The cohort was divided into two groups based on the presence (n = 49) or absence (n = 68) of pulmonary fibrosis, documented through high-resolution computer tomography. Results: The cohort comprises 117 patients, 69.23% females, with a mean age of 65.74 ± 10.19 years and abnormal body mass index (31.42 ± 5.71 kg/m2). Patients with pulmonary fibrosis have significantly higher levels of C-reactive protein (CRP) (p < 0.05), WBC (7.45 ± 7.86/mm3 vs. 9.18 ± 17.24/mm3, p = 0.053), neutrophils (4.68 ± 7.88/mm3 vs. 9.07 ± 17.44/mm3, p < 0.05), mean platelet volume (MPV) (7.22 ± 0.93 vs. 10.25 ± 0.86 fL, p < 0.05), lactate dehydrogenase (p < 0.05), and D-dimers (p < 0.05), but not ferritin (p = 0.470), reflecting the chronic proinflammatory and prothrombotic status. Additionally, patients with associated pulmonary fibrosis had a higher mean heart rate (p < 0.05) and corrected QT interval (p < 0.05). D-dimers were strongly and negatively correlated with diffusion capacity corrected for hemoglobin (DLCO corr), and ROC analysis showed that the persistence of high D-dimers values is a predictor for low DLCO values (ROC analysis: area under the curve of 0.772, p < 0.001). The results of pulmonary function tests (spirometry, body plethysmography) and the 6-minute walk test demonstrated no significant difference between groups, without notable impairment within either group. Conclusions: Patients with COVID-19-related pulmonary fibrosis have a persistent long-term proinflammatory, prothrombotic status, despite the functional recovery. The persistence of elevated D-dimer levels could emerge as a predictive factor associated with impaired DLCO.

Post-COVID changes in lung function 6 months after veno-venous extracorporeal membrane oxygenation: a prospective observational clinical trial.

Severe coronavirus disease 2019 (COVID-19) may require veno-venous extracorporeal membrane oxygenation (V-V ECMO). While V-V ECMO is offered in severe lung injury to COVID-19, long-term respiratory follow-up in these patients is missing. Therefore, we aimed at providing comprehensive data on the long-term respiratory effects of COVID-19 requiring V-V ECMO support during the acute phase of infection. In prospective observational cohort study design, patients with severe COVID-19 receiving invasive mechanical ventilation and V-V ECMO (COVID group, n = 9) and healthy matched controls (n = 9) were evaluated 6 months after hospital discharge. Respiratory system resistance at 5 and 19 Hz (R5, R19), and the area under the reactance curve (AX5) was evaluated using oscillometry characterizing total and central airway resistances, and tissue elasticity, respectively. R5 and R19 difference (R5-R19) reflecting small airway function was also calculated. Forced expired volume in seconds (FEV1), forced expiratory vital capacity (FVC), functional residual capacity (FRC), carbon monoxide diffusion capacity (DLCO) and transfer coefficient (KCO) were measured. The COVID group had a higher AX5 and R5-R19 than the healthy matched control group. However, there was no significant difference in terms of R5 or R19. The COVID group had a lower FEV1 and FVC on spirometry than the healthy matched control group. Further, the COVID group had a lower FRC on plethysmography than the healthy matched control group. Meanwhile, the COVID group had a lower DLCO than healthy matched control group. Nevertheless, its KCO was within the normal range. Severe acute COVID-19 requiring V-V ECMO persistently impairs small airway function and reduces respiratory tissue elasticity, primarily attributed to lung restriction. These findings also suggest that even severe pulmonary pathologies of acute COVID-19 can manifest in a moderate but still persistent lung function impairment 6 months after hospital discharge. NCT05812196.

Influencing Factors on Intersegmental Identification Adequacy in Segmentectomy with Intraoperative Indocyanine Green (ICG) Intravenous Administration.

Accurate identification of the intersegmental plane is essential in segmentectomy, and Indocyanine Green (ICG) assists in visualizing lung segments. Various factors, including patient-related, intraoperative, and technical issues, can influence boundary delineation. This study aims to assess the rate of unsuccessful intersegmental identification and identify the contributing factors. We analyzed cases of lung segmentectomy from April 2020 to March 2023, where intraoperative ICG was intravenously administered during robot-assisted or video-assisted thoracoscopic surgery. Cases where fluorescence extended beyond expected boundaries within 30 s were classified as the "unclear boundary group". This group was then compared to the "clear boundary group". The study encompassed 111 cases, 104 (94%) of which were classified under the "clear boundary group" and 7 (6%) under the "unclear boundary group". The "unclear boundary group" had a significantly lower DLCO (15.7 vs. 11.8, p = 0.03) and DLCO/VA (4.3 vs. 3.0, p = 0.01) compared to the "clear boundary group". All cases in the "unclear boundary group" underwent lower lobe segmentectomy. ICG administration effectively outlines pulmonary segments. Challenges in segment demarcation may occur in cases with low DLCO and DLCO/VA values, particularly during lower lobe segmentectomy.

The study of respiratory function of the lungs in patients with Bronchial Asthma

The article discusses the possibilities of functional assessment of the state of the respiratory function of the lungs in patients with bronchial asthma.The purpose of the study: a comparative assessment of the information content of capnometry, spirometry, the method of multiple breath nitrogen washout and the diffusion test in patients with asthma.Results and conclusions: 2 groups of patients were examined: I — 30 patients with asthma of 3–4 degrees of severity, II — 30 healthy volunteers. Capnometry showed a statistically significant increase in the slope of the alveolar phase in patients with asthma compared to the control group with quiet breathing, both before and after the use of a bronchodilator. According to spirometry data, in patients, the FEV1 /FVC ratio was statistically significantly lower compared to the control group, both before and after bronchodilator use. In a comparative analysis of the diffusion capacity of the lungs, there was a trend towards lower DLCO values in patients with asthma. A statistically significant difference was obtained in relation to the lung clearance index between the group of patients with asthma and the control group, in which the index was significantly lower. There were no statistically significant differences between the FRC (%) estimates obtained using the diffusion test and the method of the multiple breath nitrogen washout in patients with asthma. Thus, the informative methods in patients with asthma were not only the method of spirometry, but also the method of capnometry and the method of multiple breath nitrogen washout, which revealed uneven ventilation and distribution of ventilation-perfusion ratios in the lungs.

Predictors of reoperation after lung volume reduction surgery

ObjectivesLung volume reduction surgery (LVRS) has proven an effective treatment for emphysema, by decreasing hyperinflation and improving lung function, activity level and reducing dyspnoea. However, postoperative air leak is an important complication, often leading to reoperation.Our aim was to analyse reoperations after LVRS and identify potential predictors.MethodsConsecutive single-centre unilateral VATS LVRS performed from 2017 to 2022 were included. Typically, 3–5 minor resections were made using vascular magazines without buttressing. Data were obtained from an institutional database and analysed. Multivariable logistic regression was used to identify predictors of reoperation. Number and location of injuries were registered.ResultsIn total, 191 patients were included, 25 were reoperated (13%). In 21 patients, the indication for reoperation was substantial air leak, 3 patients bleeding and 1 patient empyema. Length of stay (LOS) was 21 (11–33) vs. 5 days (3–11), respectively. Only 3 injuries were in the stapler line, 13 within < 2cm and 15 injuries were in another site. Multivariable logistic regression analysis showed that decreasing DLCO increased risk of reoperation, OR 1.1 (1.03, 1.18, P = 0.005). Resections in only one lobe, compared to resections in multiple lobes, were also a risk factor OR 3.10 (1.17, 9.32, P = 0.03). Patients undergoing reoperation had significantly increased 30-day mortality, OR 5.52 (1.03, 26.69, P = 0.02).ConclusionsOur incidence of reoperation after LVRS was 13% leading to prolonged LOS and increased 30-day mortality. Low DLCO and resections in a single lobe were significant predictors of reoperation. The air leak was usually not localized in the stapler line.Graphical abstractKey question: What characterizes reoperations after lung volume reduction surgeries?Key findings: Lung injuries were predominantly located away from the original surgical site.Take home message: Lung injuries remote from the stapler line is frequent during reoperation after lung volume reduction surgery.Location of lung injuries found during reoperation after lung volume reduction surgery

Cohort study to evaluate prognostic factors in idiopathic pulmonary fibrosis patients introduced to oxygen therapy

While high-level evidence is lacking, numerous retrospective studies have depicted the value of supplemental oxygen in idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases, and its use should be encouraged where necessary. The clinical course and survival of patients with IPF who have been introduced to oxygen therapy is still not fully understood. The objective of this study was to clarify overall survival, factors associated with prognosis, and causes of death in IPF patients after the start of oxygen therapy. This is a prospective cohort multicenter study, enrolling patients with IPF who started oxygen therapy at 19 hospitals with expertise in interstitial lung disease. Baseline clinical data at the start of oxygen therapy and 3-year follow-up data including death and cause of death were assessed. Factors associated with prognosis were analyzed using univariable and multivariable analyses. One hundred forty-seven eligible patients, of whom 86 (59%) were prescribed ambulatory oxygen therapy and 61 (41%) were prescribed long-term oxygen therapy, were recruited. Of them, 111 died (76%) during a median follow-up of 479 days. The median survival from the start of oxygen therapy was 537 ± 74 days. In the univariable analysis, low body mass index (BMI), low forced vital capacity (FVC), low diffusion capacity (DLCO), resting hypoxemia, short 6 min-walk distance, and high COPD assessment test (CAT) score were significantly associated with poor prognosis. Multivariable analysis revealed low BMI, low FVC, low DLCO, low minimum SpO2 on 6MWT, and high CAT score were independent factors for poor prognosis. The overall survival of IPF patients after starting oxygen therapy is about 1.5 years. In addition to pulmonary function tests, 6MWT and patient reported outcomes can be used to predict prognosis more accurately.Clinical Trial Registration: UMIN000009322.

Longitudinal significance of six-minute walk test in patients with nontuberculous mycobacterial pulmonary disease: an observational study

BackgroundThe long-term exercise tolerance changes in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) are of great interest because of its chronic course. This study aimed to characterize the associations between changes over time in six-minute walking test (6MWT) parameters and clinical parameters in patients with NTM-PD.MethodsOverall, 188 patients with NTM-PD, visiting outpatient clinics at Keio University Hospital from April 2012 to March 2020 were included in the study. Data were collected using the St. George’s Respiratory Questionnaire (SGRQ), pulmonary function test (PFT), blood tests, and the 6MWT at registration and at least once after that. The association of the anchors and clinical indicators with the 6MWT parameters was assessed.ResultsThe median age [interquartile range] of the patients was 67 [63–74] years. The median baseline six-minute walk distance (6MWD) and final Borg scale (FBS) were 413 [361–470] m and 1 [0–2], respectively. In the correlation analysis, ΔSGRQ total/year (yr), Δforced vital capacity (FVC, % predicted)/yr, Δforced expiratory volume in 1 s (FEV1, % predicted)/yr, and Δdiffusing capacity for carbon monoxide (DLCO, % predicted)/yr correlated with both Δ6MWD/yr and ΔFBS/yr in the longitudinal analysis (|Rho| > 0.20). When stratified into three quantiles of changes in each anchor, the 6MWT parameters worsened over time in the bottom 25% group by mixed-effects model. Specifically, Δ6MWD was affected by SGRQ activity, SGRQ impacts, PFT (FVC, FEV1, and DLCO), and C-reactive protein (CRP). ΔFBS was affected by all SGRQ components, total score, and PFT. Anchor scores and variables at baseline that worsened Δ6MWD were higher SGRQ scores, lower FVC (% predicted), lower DLCO (% predicted), higher Krebs von den Lungen-6, old age, and undergoing treatment at registration. Similarly, these clinical parameters and elevated CRP, excluding undergoing treatment at registration, worsened ΔFBS.ConclusionsThe decreased walking distance and exacerbation of dyspnea on exertion over time in patients with NTM-PD may reflect a deterioration of health-related quality of life and pulmonary function. Thus, the change in 6MWT over time can be used as an indicator to accurately assess the patient’s condition and tailor their healthcare environment.

Tobacco smoking is associated with combined pulmonary fibrosis and emphysema and worse outcomes in interstitial lung disease.

Tobacco smoking is an established cause of pulmonary disease whose contribution to interstitial lung disease (ILD) is incompletely characterized. We hypothesized that compared with nonsmokers, subjects who smoked tobacco would differ in their clinical phenotype and have greater mortality. We performed a retrospective cohort study of tobacco smoking in ILD. We evaluated demographic and clinical characteristics, time to clinically meaningful lung function decline (LFD), and mortality in patients stratified by tobacco smoking status (ever vs. never) within a tertiary center ILD registry (2006-2021) and replicated mortality outcomes across four nontertiary medical centers. Data were analyzed by two-sided t tests, Poisson generalized linear models, and Cox proportional hazard models adjusted for age, sex, forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), ILD subtype, antifibrotic therapy, and hospital center. Of 1,163 study participants, 651 were tobacco smokers. Smokers were more likely to be older, male, have idiopathic pulmonary fibrosis (IPF), coronary artery disease, CT honeycombing and emphysema, higher FVC, and lower DLCO than nonsmokers (P < 0.01). Time to LFD in smokers was shorter (19.7 ± 20 mo vs. 24.8 ± 29 mo; P = 0.038) and survival time was decreased [10.75 (10.08-11.50) yr vs. 20 (18.67-21.25) yr; adjusted mortality HR = 1.50, 95%CI 1.17-1.92; P < 0.0001] compared with nonsmokers. Smokers had 12% greater odds of death for every additional 10 pack yr of smoking (P < 0.0001). Mortality outcomes remained consistent in the nontertiary cohort (HR = 1.51, 95%CI = 1.03-2.23; P = 0.036). Tobacco smokers with ILD have a distinct clinical phenotype strongly associated with the syndrome of combined PF and emphysema, shorter time to LFD, and decreased survival. Smoking prevention may improve ILD outcomes.NEW & NOTEWORTHY Smoking in ILD is associated with combined pulmonary fibrosis and emphysema and worse clinical outcomes.

Gas Exchange in Patients with Pulmonary Tuberculosis: Relationships with Pulmonary Poorly Communicating Fraction and Alveolar Volume

Tuberculosis-related lung damage is very different. Lung ventilation disorders have been studied in patients with pulmonary tuberculosis (TB) during the active process and after treatment, but the main causes of gas exchange changes have not been sufficiently studied. Investigation of diffusing lung capacity in combination with bodyplethysmography is useful for the interpretation of pulmonary gas exchange disorders. The aim was to determine the relationship of gas exchange with the value of alveolar volume (VA) and pulmonary poorly communicating fraction (PCF) in patients with pulmonary TB. A total of 292 patients (117/175 M/W) with verified pulmonary TB with smoking age less than 10 packs-years underwent spirometry, bodyplethysmography, and DLCO by the single-breath method. PCF was estimated calculating the difference between total lung capacity (TLC) and VA (% TLC). Patients with low DLCO had statistically significantly lower spirometric values (FVC, FEV1, FEV1/FVC, MMEF), lower TLC, higher airway resistance, RV/TLC, air-trapping volume, and PCF. The patients with low level of DLCO were divided into four groups depending on level VA and PCF. In most patients with infiltrative tuberculosis (50%), the leading syndrome of the DLCO decrease was alveolar-capillary damage. In patients with tuberculomas, the syndromes of alveolar capillary damage and pulmonary ventilation inhomogeneity were with the same frequency (43%). In patients with disseminated tuberculosis, the most frequent syndrome of the DLCO decrease was pulmonary ventilation inhomogeneity (33%), then alveolar-capillary damage (29%) and mixed (24%). In patients with cavernous tuberculosis, the leading syndrome of the DLCO decrease was mixed (39%), then alveolar capillary damage (25%) and pulmonary ventilation inhomogeneity (23%). The syndrome of gas exchange surface reduction in patients with disseminated and cavernous tuberculosis was less common (14%). In conclusion, an additional evaluation of the combination of PCF and VA increases the amount of clinical information obtained using the diffusion lung capacity measurements, since it allows identifying various syndromes of gas exchange impairment. The leading causes of diffusing capacity impairment vary by different types of pulmonary TB.

Association between Parenchymal B-Cell Follicles and CT-Proven Enlarged Mediastinal Lymph Nodes in Patients with Pulmonary Fibrosis

Background: Mediastinal lymph node enlargement (MLNE) is a finding described in a subset of patients with idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs) and is associated with accelerated disease progression and increased mortality. The cause of MLNE is still not known. Our hypothesis is that there is an association between MLNE and B-cell follicles in lung tissue, another aspect detectable in the lung tissue of patients with IPF and other ILDs. Objectives: The aim of this study was to assess if there is an association between MLNE and B-cell follicles in lung tissue in patients with IPF and other ILDs. Method: Patients having transbronchial cryobiopsies performed as part of an investigation for ILD were included in this prospective observational study. MLNE (smallest diameter ≥10 mm) were assessed in station 7, 4R, and 4L on high-resolution computed tomography scans. B-cell follicles were assessed on haematoxylin-eosin-stained specimens. Lung function, 6-minute walk test, acute exacerbation, and mortality were registered after 2 years. In addition, we investigated if the finding of B-cell follicles was consistent in patients who underwent both surgical lung biopsies (SLBs) and cryobiopsies. Results: In total, 93 patients were included for analysis (46% diagnosed with IPF, 54% diagnosed with other ILDs). MLNE was found in 26 (60%) of the IPF patients and in 23 (46%) of the non-IPF patients (p = 0.164). Diffusing capacity for carbon monoxide was significantly lower (p = 0.03) in patients with MLNE compared to patients without MLNE. B-cell follicles were found in 11 (26%) of the IPF patients and in 22 (44%) of the non-IPF patients (p = 0.064). Germinal centres were not seen in any of the patients. There was no association between MLNE and B-cell follicles (p = 0.057). No significant difference in change of pulmonary function test was seen at 2-year follow-up when comparing the patients with and without MLNE or B-cell follicles. In 13 patients, both SLBs and cryobiopsies were performed. The presence of B-cell follicles was not consistent when comparing the two different methods. Conclusion: MLNE is evident in a substantial part of patients with ILD and is associated with lower DLCO at inclusion. We could not demonstrate an association between histological B-cell follicles in biopsies and MLNE. A possible explanation for this is that the cryobiopsies might not have captured the changes we sought.

Pulmonary circulation abnormalities in post-acute COVID-19 syndrome: dual-energy CT angiographic findings in 79 patients.

To evaluate the frequency and pattern of pulmonary vascular abnormalities in the year following COVID-19. The study population included 79 patients remaining symptomatic more than 6months after hospitalization for SARS-CoV-2 pneumonia who had been evaluated with dual-energy CT angiography. Morphologic images showed CT features of (a) acute (2/79; 2.5%) and focal chronic (4/79; 5%) PE; and (b) residual post COVID-19 lung infiltration (67/79; 85%). Lung perfusion was abnormal in 69 patients (87.4%). Perfusion abnormalities included (a) perfusion defects of 3 types: patchy defects (n = 60; 76%); areas of non-systematized hypoperfusion (n = 27; 34.2%); and/or PE-type defects (n = 14; 17.7%) seen with (2/14) and without (12/14) endoluminal filling defects; and (b) areas of increased perfusion in 59 patients (74.9%), superimposed on ground-glass opacities (58/59) and vascular tree-in-bud (5/59). PFTs were available in 10 patients with normal perfusion and in 55 patients with abnormal perfusion. The mean values of functional variables did not differ between the two subgroups with a trend toward lower DLCO in patients with abnormal perfusion (74.8 ± 16.7% vs 85.0 ± 8.1). Delayed follow-up showed CT features of acute and chronic PE but also two types of perfusion abnormalities suggestive of persistent hypercoagulability as well as unresolved/sequelae of microangiopathy. Despite dramatic resolution of lung abnormalities seen during the acute phase of the disease, acute pulmonary embolism and alterations at the level of lung microcirculation can be identified in patients remaining symptomatic in the year following COVID-19. • This study demonstrates newly developed proximal acute PE/thrombosis in the year following SARS-CoV-2 pneumonia. • Dual-energy CT lung perfusion identified perfusion defects and areas of increased iodine uptake abnormalities, suggestive of unresolved damage to lung microcirculation. • This study suggests a complementarity between HRCT and spectral imaging for proper understanding of post COVID-19 lung sequelae.

Pulmonary Vascular Volume by Quantitative CT in Dyspneic Smokers with Minor Emphysema

Reduced lung diffusing capacity for carbon monoxide (DLCO) at rest and increased ventilation (⩒ E)-carbon dioxide output (⩒CO2) during exercise are frequent findings in dyspneic smokers with largely preserved FEV1. It remains unclear whether low DLCO and high ⩒ E-⩒CO2 are mere reflections of alveolar destruction (i.e. emphysema) or impaired pulmonary perfusion in non-emphysematous tissue contributes to these functional abnormalities. Sixty-four smokers (41 males, FEV1= 84 ± 13%predicted) underwent pulmonary function tests, an incremental exercise test, and quantitative chest computed tomography. Total pulmonary vascular volume (TPVV) was calculated for the entire segmented vascular tree (VIDA Vision™). Using the median % low attenuation area (-950 HU), participants were dichotomized into “Trace” or “Mild” emphysema (E), each group classified into preserved versus reduced DLCO. Within each emphysema subgroup, participants with abnormally low DLCO showed lower TPVV, higher ⩒ E-⩒CO2, and exertional dyspnea than those with preserved DLCO (p < 0.05). TPVV (r = 0.34; p = 0.01), but not emphysema (r = −0.05; p = 0.67), correlated with lower DLCO after adjusting for age and height. Despite lower emphysema burden, Trace-E participants with reduced DLCO had lower TPVV, higher dyspnea, and lower peak work rate than the Mild-E with preserved DLCO (p < 0.05). Interestingly, TPVV (but not emphysema) correlated inversely with both dyspnea-work rate (r = −0.36, p = 0.004) and dyspnea-⩒ E slopes (r = −0.40, p = 0.001). Reduced pulmonary vascular volume adjusted by emphysema extent is associated with low DLCO and heightened exertional ventilation in dyspneic smokers with minor emphysema. Impaired perfusion of non-emphysematous regions of the lungs has greater functional and clinical consequences than hitherto assumed in these subjects.

Low diffusion capacity predicts poor prognosis in extensive stage small cell lung cancer: a single-center analysis of 10 years

BackgroundPoor pulmonary function and chronic obstructive pulmonary disease (COPD) are associated with poorer overall survival (OS) in non-small-cell lung cancer (NSCLC) patients. Few studies have investigated the association between pulmonary function and OS in small-cell lung cancer (SCLC) patients. We compared the clinical characteristics of extensive disease SCLC (ED-SCLC) with or without moderately impaired diffusion capacity for carbon monoxide (DLco) and investigated the factors associated with survival in ED-SCLC patients.MethodsThis retrospective single-center study was performed between January 2011 and December 2020. Of the 307 SCLC patients who received cancer therapy during the study, 142 with ED-SCLC were analyzed. The patients were divided into DLco < 60% group and DLco ≥ 60% groups. OS and predictors of poor OS were analyzed.ResultsThe median OS of the 142 ED-SCLC patients was 9.3 months and the median age was 68 years. In total, 129 (90.8%) patients had a history of smoking, and 60 (42.3%) had COPD. Thirty-five (24.6%) patients were assigned to the DLco < 60% group. Multivariate analysis revealed that DLco < 60% (odds ratio [OR], 1.609; 95% confidence interval [CI], 1.062–2.437; P = 0.025), number of metastases (OR, 1.488; 95% CI, 1.262–1.756; P < 0.001), and < 4 cycles of first-line chemotherapy (OR, 3.793; 95% CI, 2.530–5.686; P < 0.001) were associated with poor OS. Forty (28.2%) patients received < 4 cycles of first-line chemotherapy; the most common reason for this was death (n = 22, 55%) from grade 4 febrile neutropenia (n = 15), infection (n = 5), or massive hemoptysis (n = 2). The DLco < 60% group had a shorter median OS than the DLco ≥ 60% group (10.6 ± 0.8 vs. 4.9 ± 0.9 months, P = 0.003).ConclusionsIn this study, approximately one quarter of the ED-SCLC patients had DLco < 60%. Low DLco (but not forced expiratory volume in 1 s or forced vital capacity), a large number of metastases, and < 4 cycles of first-line chemotherapy were independent risk factors for poor survival outcomes in patients with ED-SCLC.

Prognostication of progressive pulmonary fibrosis in connective tissue disease-associated interstitial lung diseases: A cohort study.

Connective tissue diseases-associated interstitial lung disease (CTD-ILD) is a heterogeneous condition that impairs quality of life and is associated with premature death. Progressive pulmonary fibrosis (PPF) has been identified as an important risk factor for poor prognosis. However, different criteria for PPF are used in clinical studies, which may complicate comparison between trials and translation of study findings into clinical practice. This is a retrospective single center study in patients with CTD-ILD. The prognostic relevance of PPF definitions, including INBUILD, ATS/ERS/JRS/ALAT 2022, and simplified progressive fibrosing (simplified PF) criteria, were examined in this cohort and validated in the other reported Dutch CTD-ILD cohort. A total of 230 patients with CTD-ILD were included and the median follow-up period was six (3-9) years. Mortality risk was independently associated with age (adjusted HR 1.07, p < 0.001), smoking history (adjusted HR 1.90, p = 0.045), extent of fibrosis on high-resolution computed tomography (HRCT) at baseline (adjusted HR 1.05, p = 0.018) and baseline DLCO (adjusted HR 0.97, p = 0.013). Patients with regular pulmonary function tests in the first 2 years (adjusted HR 0.42, p = 0.002) had a better survival. The prognostic relevance for survival was similar between the three PPF criteria in the two cohorts. Higher age, smoking, increased extent of fibrosis and low baseline DLCO were associated with poor prognosis, while regular pulmonary function evaluation was associated with better survival. The INBUILD, ATS/ERS/JRS/ALAT 2022, and simplified PF criteria revealed similar prognostication.

Effect of Altitude on Respiratory Functional Status in COVID-19 Survivors: Results from a Latin American Cohort-FIRCOV.

Laura Gochicoa-Rangel, Santiago C. Arce, Carlos Aguirre-Franco, Wilmer Madrid-Mejía, Mónica Gutiérrez-Clavería, Lorena Noriega-Aguirre, Patricia Schonffeldt-Guerrero, Agustín Acuña-Izcaray, Arturo Cortés-Telles, Luisa Martínez-Valdeavellano, Federico Isaac Hernández-Rocha, Omar Ceballos-Zúñiga, Rodrigo Del Rio Hidalgo, Sonia Sánchez, Erika Meneses-Tamayo, and Iván Chérrez-Ojeda; and on Behalf of the Respiratory Physiology Project in COVID-19 (FIRCOV). Effect of altitude on respiratory functional status in COVID-19 survivors: results from a Latin American Cohort-FIRCOV. High Alt Med Biol 24:37-48, 2023. Persistent symptoms and lung function abnormalities are common in COVID-19 survivors. Objectives: To determine the effect of altitude and other independent variables on respiratory function in COVID-19 survivors. Methods: Analytical, observational, cross-sectional cohort study done at 13 medical centers in Latin America located at different altitudes above sea level. COVID-19 survivors were invited to perform pulmonary function tests at least 3 weeks after diagnosis. Results: 1,368 participants (59% male) had mild (20%), moderate (59%), and severe (21%) disease. Restriction by spirometry was noted in 32%; diffusing capacity of the lung for carbon monoxide (DLCO) was low in 43.7%; and 22.2% walked less meters during the 6-minute walk test (6-MWT). In multiple linear regression models, higher altitude was associated with better spirometry, DLCO and 6-MWT, but lower oxygen saturation at rest and during exercise. Men were 3 times more likely to have restriction and 5.7 times more likely to have a low DLCO. Those who had required mechanical ventilation had lower DLCO and walked less during the 6-MWT. Conclusions: Men were more likely to have lower lung function than women, even after correcting for disease severity and other factors. Patients living at a higher altitude were more likely to have better spirometric patterns and walked farther but had lower DLCO and oxygen saturation.

Oxygenated hemoglobin as prognostic marker among patients with systemic sclerosis screened for pulmonary hypertension

Oxygenated hemoglobin (OxyHem) in arterial blood may reflect disease severity in patients with systemic sclerosis (SSc). The aim of this study was to analyze the predictive value of OxyHem in SSc patients screened for pulmonary hypertension (PH). OxyHem (g/dl) was measured by multiplying the concentration of hemoglobin with fractional oxygen saturation in arterialized capillary blood. Prognostic power was compared with known prognostic parameters in SSc using uni- and multivariable analysis. A total of 280 SSc patients were screened, 267 were included in the analysis. No signs of pulmonary vascular disease were found in 126 patients, while 141 patients presented with mean pulmonary arterial pressure ≥ 21 mmHg. Interstitial lung disease (ILD) was identified in 70 patients. Low OxyHem ≤ 12.5 g/dl at baseline was significantly associated with worse survival (P = 0.046). In the multivariable analysis presence of ILD, age ≥ 60 years and diffusion capacity for carbon monoxide (DLCO) ≤ 65% were negatively associated with survival. The combination of low DLCO and low OxyHem at baseline could predict PH at baseline (sensitivity 76.1%). This study detected for the first time OxyHem ≤ 12.5 g/dl as a prognostic predictor in SSc patients. Further studies are needed to confirm these results.

Anatomic lung resection after immune checkpoint inhibitors for initially unresectable advanced-staged non-small cell lung cancer: a retrospective cohort analysis.

Patients with initially unresectable advanced non-small cell lung cancer (NSCLC) might experience prolonged responses under immune checkpoint inhibitors (ICIs). In this setting, Multidisciplinary Tumor Board (MTB) seldomly suggest surgical resection of the primary tumor with the ultimate goal to eradicate macroscopic residual disease. Our objective was to report the perioperative outcomes of patients who underwent anatomic lung resection in these infrequent circumstances. We set a retrospective multicentric single arm study, including all patients with advanced-staged initially unresectable NSCLC (stage IIIB to IVB) who received systemic therapy including ICIs and eventually anatomical resection of the primary tumor in 10 French thoracic surgery units from January 2016 to December 2020. Coprimary endpoints were in-hospital mortality and morbidity. Secondary endpoints were the rate of complete resection of the pulmonary disease, major pathologic response, risk factors associated with post-operative complications, and overall survival. Twenty-one patients (median age 64, female 62%) were included. Eighteen patients (86%) progressed after first line chemotherapy and received second line ICI. The median time between diagnosis and surgery was 22 months [interquartile range (IQR) 18-35 months]. Minimally-invasive approach was used in 10 cases (48%), with half of these requiring conversion to open thoracotomy. Nine patients (43%) presented early post-operative complications, and one patient died from broncho-pleural fistula one month after surgery. Rates of complete resection of the pulmonary disease and major pathologic response were 100% and 43%, respectively. In univariable analysis, diffusing capacity for carbon monoxide (DLCO) was the only factor associated with the occurrence of postoperative complications (P=0.027). After a median follow-up of 16.0 months after surgery (IQR, 12.0-30.0 months), 19 patients (90%) were still alive. Anatomic lung resections appear to be a reasonable option for initially unresectable advanced NSCLC experiencing prolonged response under ICIs. Nonetheless, minimally invasive techniques have a low applicability and post-operative complications remains higher in patients who had lower DLCO values. The late timing of surgery may also contribute to complications.