DLCO Research Articles

Pulmonary diffusing capacity among individuals recovering from mild to moderate COVID-19: a cross-sectional study

Impaired pulmonary diffusing capacity for carbon monoxide (DLCO) following COVID-19 has been consistently reported among individuals recovering from severe-critical infection. However, most long COVID cases follow non-severe COVID-19. We assessed DLCO among individuals with long COVID recovering from mild to moderate acute illness. A cross-sectional study of adults with long COVID, assessed at a COVID recovery clinic > 3 months following the onset of acute infection, during 2020–2021. Participants subjectively ranked their dyspnea severity based on its impact on their daily living and underwent comprehensive pulmonary function testing (PFT). Clinical correlates for impaired DLCO (defined as < 80%) were assessed using multivariable logistic regression models. A total of 458 individuals, their mean age 45 (SD 16) and 246 (54%) of whom are women, were evaluated at an average of ~ 4 months following acute COVID-19. The most frequent PFT impairment was reduced DLCO, identified among 67 (17%) of the cohort. Clinical correlates of impaired DLCO included women (odds ration [OR] 3.64, 95% confidence interval [CI] 1.78–7.45, p < 0.001), cigarette smoking (OR 2.25, 95% CI 1.14–4.43, p = 0.019), and moderate-severe dyspnea (OR 2.77, 95% CI 1.39–5.50, p = 0.004). BMI inversely correlated with DLCO (OR 0.90, 95% CI 0.85–0.96 per 1 unit, p = 0.002). Impaired DLCO was not uncommon among individuals recovering from mild to moderate COVID-19. Women are at a greater risk, and subjective dyspnea correlated with impaired DLCO. Clinicians can rely on self-reported significant dyspnea to guide further assessment.

Usefulness of monitoring mycophenolic acid exposure in systemic sclerosis-related interstitial lung disease: a retrospective cohort study

BackgroundSystemic sclerosis-related interstitial lung disease (SSc-ILD) represents a significant cause of morbidity and mortality in Systemic Sclerosis (SSc). Mycophenolate mofetil (MMF) is currently the first line treatment for SSc-ILD. There is no recommendation on the dosage of mycophenolic acid (MPA) blood concentrations, so we aimed to study the correlation between MPA exposure and respiratory outcomes in this population.MethodsWe conducted a retrospective cohort study of SSc-ILD patients treated with MMF in our center. According to our policy, a complete patient evaluation was performed approximately one year after MMF initiation, during which the mycophenolic acid (MPA) residual rate (RR) was measured. We analyzed the association between RR and changes in forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) over time.ResultsForty-three SSc-ILD patients were included. Patients with higher RR levels (≥ 1.5 mg/L) had a significantly better FVC evolution with a higher proportion of stabilization and lower proportion of FVC decrease (p = 0.024). RR above 1.5 mg/L was a predictive factor of reduced FVC decline compared with lower RR levels adjusting for MMF dose and duration of MMF exposure (p = 0.008). There was no difference regarding DLCO outcome.ConclusionOur study suggests that optimal MPA exposure, as indicated by RR levels, may better protect against FVC decline in SSc-ILD patients treated with MMF. Routine monitoring of MPA exposure could be beneficial in optimizing treatment outcomes. Prospective, multicenter studies are needed to further explore the relationship between MPA exposure and clinical outcomes in SSc-ILD.

A decision rule for identifying patients at high risk for impaired lung diffusion capacity after COVID-19

Aim. To elaborate a decision rule for identifying the main predictors of impaired lung diffusion capacity after COVID-19. Materials and methods. The retrospective study included 341 patients without underlying lung diseases (median age 48 years) who experienced COVID-19 with bilateral pneumonia. The median extent of parenchymal lesion in the acute phase of COVID-19 (CTmax) was 50%. Spirometry, body plethysmography, and lung diffusion capacity for carbon monoxide (DLCO) test were performed. The data were analyzed by descriptive statistics, correlation analysis, one-dimensional logistic regression analysis with an assessment of odds ratios (OR), and multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to assess the quality of the binary classifier model.Results. The initial model for predicting reduced DLCO (&lt; 80% of predicted) included the following predictors: CTmax, time interval from the COVID-19 onset, gender, age, body mass index. Backward stepwise regression was applied, and a binary classifier model that includes CTmax was obtained. The sensitivity and specificity of the model for the training sample were 80 and 67%, respectively, for the test sample – 79 and 70%, respectively. The analysis of OR showed that OR &gt; 1 was observed at СTmax &gt; 40%.Conclusion. The decision rule was obtained for predicting impaired lung diffusion capacity after COVID-19 with virus-associated lung damage in patients without underlying bronchopulmonary diseases. Patients with CTmax &gt; 40% require more thorough clinical follow-up with DLCO monitoring after the acute phase of COVID-19

Why do patients stay in hospital after enhanced recovery thoracoscopic wedge resection? A prospective observational study.

This single-centre prospective observational study aimed to investigate reasons for prolonged hospitalization [over the median length of stay (LOS)] after enhanced recovery thoracoscopic [ERAS 3-port video-assisted thoracoscopic surgery (VATS)] wedge resection. All patients were evaluated twice-daily by an investigator for reasons of hospitalization. Each reason was analysed individually. Predictors for prolonged hospitalization were identified using a multivariable backward stepwise logistic regression model. A total of 150 consecutive patients (lymphadenectomy 8.7%) were included from November 2022 to December 2023, with a median LOS of 1 (interquartile range 1-2) day. Of these, 55 patients (36.7%) experienced prolonged hospitalization. The main reasons included postoperative pain (16.0%), air leak (14.7%) and social factors (14.7%), followed by oxygen dependency (7.3%), gastrointestinal factors (5.3%), urinary factors (4.7%), pneumonia (1.3%), pleural effusion (1.3%), chylothorax (0.7%), atrial fibrillation (0.7%), confusion (0.7%) and fatigue (0.7%). Multivariable analysis revealed that an increase in the percentage of predicted forced expiratory volume in 1 s (FEV1%pre) by 1% [odds ratio (OR) 0.41, P = 0.023) and percentage of predicted diffusing capacity for carbon monoxide (DLCO%pre) by 1% (OR 0.95, P = 0.002) decreased likelihood of prolonged hospitalization. Conversely, each additional pack-year (OR 1.01, P = 0.028) and living alone (OR 3.55, P = 0.005) increased the risk of prolonged hospitalization. Prolonged hospitalization (LOS > 1 day) after ERAS 3-port VATS wedge resection, with 8.7% lymphadenectomy, was mainly due to pain, air leak and social factors. Smokers with decreased FEV1%pre or DLCO%pre and patient living alone were at increased risk. ClinicalTrials.gov: NCT06118593 (https://clinicaltrials.gov/study/NCT06118593?cond=why%20in%20hospital&rank=2).

Insights into sex differences in perioperative outcomes of non-small cell lung cancer patients.

The appreciation of sex differences is substantial for precise cancer management. Surgery is the main treatment for non-small cell lung cancer (NSCLC). We aimed to identify sex differences on perioperative outcomes in NSCLC patients and to uncover the origins of sex effect in outcomes using a Chinese cohort. We retrospectively enrolled patients undergoing NSCLC surgery in the Western China Lung Cancer Database from January 2014 to April 2021. We compared baseline characteristics and perioperative outcomes between male and female. Multivariable analyses were performed. We conducted causal mediation analysis to identify drivers to sex differences in perioperative outcomes. Altogether, data of 10,181 patients (5,738 women and 4,443 men) were analyzed. Women had lower incidence of complications (5.05% vs. 12.15%), shorter postoperative length of stays (4.92 vs. 6.41 days), and less hospitalization cost (50,713.69 vs. 54,580.85, Chinese Yuan). Multivariable regression analysis identified sex as an independent factor of perioperative complications [odds ratio (OR), 1.843, 95% confidence interval (CI): 1.476-2.294], as well as of postoperative length of hospital stays (beta 0.123, 95% CI: 0.099-0.148), and hospitalization cost (beta 0.026, 95% CI: 0.026-0.026). Mediation analysis revealed that age, body mass index, prevalence of chronic obstructive pulmonary disease, predicted diffusion capacity for carbon monoxide, tumor size, pleural adhesion, and surgery duration were identified as mediators for sex differences in outcomes, while smoking status, surgery type, and resection extent were not. Female NSCLC patients demonstrated lower incidence of complications, shorter postoperative length of stays, and less hospitalization cost after surgery. Those differences between men and women could be explained by their inherent biological differences and baseline health status. Perioperative management strategies for NSCLC should prioritize recognizing the potentially poorer outcomes among male patients and implementing tailored precautions accordingly.

Reference equations for DLNO and DLCO in Mexican Hispanics: influence of altitude and race

ObjectivesThis study aimed to evaluate pulmonary diffusing capacity for nitric oxide (DLNO) and pulmonary diffusing capacity for carbon monoxide (DLCO) in Mexican Hispanics born and raised at 2240 m altitude...

Pulmonary Vascular Structure and Function Are Related to Exercise Capacity in Health and COPD

Although it is generally accepted that aerobic exercise training does not change lung structure or function, some work suggests that greater pulmonary vascular structure and function is associated with higher exercise capacity (VO2peak). Is there a cross-sectional association between the pulmonary vasculature and VO2peak? We hypothesized that those with higher computed tomography (CT) blood vessel volumes, and pulmonary diffusing capacity for carbon monoxide (DLCO) would have higher VO2peak, independent of airflow limitation. Participants from the CanCOLD study were categorized as: never-smokers with normal spirometry (n=263); ever-smokers with normal spirometry (n=407); and chronic obstructive pulmonary disease (COPD): individuals with spirometric airflow obstruction (n=334). Total vessel volume (TVV), the volume for all vessels with a cross-sectional area ≤5 mm2 (BV5), and between 5-10 mm2 (BV5-10) were generated from CT scans and used as indices of pulmonary vascular structure. DLCO was used as an index of pulmonary microvascular function. VO2peak was evaluated via incremental cardiopulmonary exercise testing. General linear regression models revealed that even after controlling for FEV1, emphysema severity and body morphology, DLCO, TVV, BV5 and BV5-10, were independently associated with VO2peak. Interaction effects were observed between COPD and TVV, BV5, and BV5-10 indicating a weaker association between pulmonary vascular volumes and VO2peak in COPD. Our results suggest that pulmonary vascular structure and DLCO is independently associated with VO2peak, regardless of severity of airflow limitation and emphysema, suggesting that these associations are not limited to COPD.

COPD associated pulmonary hypertension: A post hoc analysis of the PERFECT study.

The PERFECT study, a randomized, controlled, double-blind study of inhaled treprostinil in patients with COPD and associated pulmonary hypertension (PH-COPD) was a negative trial that was terminated early. The reason(s) for the negative outcome remains uncertain. A post hoc analysis of data from the PERFECT study was undertaken to identify adverse responders and possibly potential responders. The goal was also to provide insight into phenotypes for possible inclusion and exclusion in future PH-COPD clinical trials. An adverse response on active treatment was seen in 36.4% (24/66) of the subjects compared to 27.6% (16/58) on placebo. There was no evidence to suggest that hyperinflation, bronchospasm, or occult heart failure played any role in the untoward outcomes of the study. The patients who died during the study all had baseline diffusing capacity for carbon monoxide ≤25% of predicted. Evidence of a potential response was seen in 10.6% (7/66) of the patients who received inhaled treprostinil. Patients who had evidence of a treatment response had a baseline mean pulmonary artery pressure of ≥40 mmHg and a forced expiratory volume in the first second of ≥40%. Change in N-terminal prohormone of brain natriuretic peptide did not predict clinical response. This post hoc analysis provides information that may potentially enable improved selection of patients for future therapeutic trials in PH-COPD. These analyses are post hoc, observational, and exploratory. The thresholds defining the spectrum of responders are preliminary and may require further refinement and validation in future studies.

Efficacy and safety of oral versus intravenous cyclophosphamide in treatment of connective tissue disease-related interstitial lung disease.

Interstitial lung disease (ILD) resulting from connective tissue disease (CTD) greatly undermines people's health. Cyclophosphamide (CYC) is a widely used agent in treating CTD-ILD. We compared the efficacy and safety of oral and intravenous CYC in CTD-ILD treatment. The retrospectively enrolled CTD-ILD patients were divided into the oral and intravenous CYC groups. The chest high-resolution computed tomography examination, forced vital capacity (FVC), lung carbon monoxide diffusion capacity (Dlco) determinations, and 6 min walk test (6MWT) were performed pre-treatment and at the 3rd, 6th, and 12th months posttreatment. Radiographic ILD severity was assessed using the Warrick score. Krebs Von den Lungen-6, surfactant protein A (SP-A), SP-D, and erythrocyte sedimentation rate (ESR) before and at the 12th month post-treatment were determined. CYC cumulative dose and occurrence of adverse reactions during treatment were recorded. CYC cumulative dose in the intravenous CYC group was reduced. Compared with oral CYC treatment, intravenous CYC caused decreased Warrick score and increased FVC and 6MWT at the 6th month, and elevated DLco at the 3rd and 6th months posttreatment. SP-A, SP-D and ESR levels in both groups were reduced 12 months posttreatment, with a more evident decrease in the intravenous CYC group. Intravenous CYC had lower total adverse reaction incidence. Compared with oral CYC, intravenous CYC decreases Warrick score and increases FVC and 6MWT at 6 months posttreatment, and reduces SP-A, SP-D, and ESR levels after 12 months of treatment, which shows low CYC cumulative dose and adverse reaction incidence in treating CTD-ILD.

Correlation of the severity of the clinical presentation of SARS-CoV-2 pneumonia with respiratory function parameters in the post-COVID period.

Since COVID-19 first surfaced in 2019, it has seriously threatened public health. The most prevalent symptoms are respiratory ones. This study aimed to present the correlation between the severity of the clinical presentation of the disease and the results of respiratory function tests conducted within 6 months after hospital discharge. This retrospective study included 99 patients with confirmed SARS-CoV-2 virus infection. Of all patients 24.2% had accentuated bronchovascular pattern, 9.1% had unilateral, and 29.3% had bilateral pneumonia. In comparison, 35.4% patients had diffuse changes, which were described as acute respiratory distress syndrome (ARDS) on computed tomography (CT). Patients with unilateral, bilateral pneumonia or diffuse lung damage had significantly lower forced vital capacity (FVC) values. They were treated with non-invasive mechanical ventilation (NIV) or invasive mechanical ventilation (MV) and had lower FVC values (0.039). A negative, weak correlation existed between CT findings during the infection and Diffusing capacity for carbon monoxide (DLCO) measured after the infection (0.003). A negative, weak correlation was found between oxygen therapy, the use of NIV, and MV findings during the infection with DLCO. A negative correlation was noted between leukocyte values during the infection and forced expiratory volume in the first second (FEV1) and FVC after the infection. Patients with COVID-19 infection who need oxygen support and MV continue to suffer from loss of respiratory function after the resolution of COVID-19 infection. These findings highlight the negative predictive value of pulmonary tests in the long-term follow-up for the development of PC-ILD as well as decreased pulmonary capacity.

Assessing health-related quality of life in patients with interstitial lung diseases

BackgroundThe R-Scale-PF was proposed to evaluate the health-related quality of life (HRQoL) in patients with idiopathic pulmonary fibrosis (IPF). We generated a German version of the R-Scale-PF (GR-Scale), representing the first translation of the questionnaire into another language and assessed HRQoL longitudinally in various interstitial lung diseases (ILDs) using the R-Scale-PF scoring system at a specialized ILD centre.MethodsWe have translated the questionnaire in accordance with the WHO translation guidelines and applied it to 80 ILD patients of our department, with follow-ups after 3–6 months, assessing its internal consistency, floor and ceiling effects, concurrent validity, known-groups validity, and its responsiveness to changes over time.ResultsAt baseline, all 80 patients completed the GR-Scale. In 70 patients (87.5%), follow-up data could be obtained after 4.43 ± 1.2 months. The GR-Scale demonstrated acceptable internal consistency (Cronbach’s α 0.749) and slight floor effects. Concurrent validity analysis showed weak but significant correlations with forced vital capacity (FVC; r=-0.282 p = 0.011) and diffusion capacity for carbon monoxide (DLco; r=-0.254 p = 0.025). In the follow-up analysis, moderate correlations were found with FVC (r=-0.41 p < 0.001) and DLco (r=-0.445 p < 0.001). No significant difference in the total score was found between patients with IPF (n = 10) and with non-IPF ILDs (n = 70). The GR-Scale successfully discriminated between groups of varying disease severity based on lung function parameters and the need for long-term oxygen therapy (LTOT). Furthermore, it was able to distinguish between patients showing improvement, stability or decline of lung function parameters.ConclusionOur prospective observational pilot study suggests that the GR-Scales is a simple and quick tool to measure HRQoL in patients with ILDs, thus providing an important additional information for the clinical assessment of ILD patients.Trial registrationOur study was retrospectively registered in the German Clinical Trial Register (DRKS) on 02.11.2022 (DRKS-ID: DRKS00030599).

Impact of a 12-week high-intensity interval training intervention on cardiac structure and function after COVID-19 at 12-month follow-up.

In patients previously hospitalised for COVID-19, a 12-week high-intensity interval training (HIIT) intervention has previously been shown to increase left ventricular mass (LVM) immediately after the intervention. In the present study, we examined the effects of the same HIIT scheme on LVM, pulmonary diffusing capacity, symptom severity and functional capacity at 12-month follow-up. In this investigator-blinded, randomised controlled trial, 12weeks of a supervised HIIT scheme (4×4min, three times a week) was compared to standard care (control) in patients recently discharged from hospital due to COVID-19. At inclusion and at 12-month follow-up, LVM was assessed by cardiac magnetic resonance imaging (cMRI, primary outcome), while pulmonary diffusing capacity for carbon monoxide (DLCOc, secondary outcome) was examined by the single-breath method. Symptom severity and functional status were examined by the Post-COVID-19 Functional Scale (PCFS) and King's Brief Interstitial Lung Disease (KBILD) questionnaire score. Of the 28 patients assessed at baseline, 22 completed cMRI at 12-month follow-up (12.4±0.6months after inclusion). LVM was maintained in the HIIT but not the standard care group, with a mean between-group difference of 9.68 [95% CI: 1.72, 17.64] g (P=0.0182). There was no differences in change from baseline to 12-month follow-up between groups in DLCOc % predicted (-2.45 [-11.25, 6.34]%; P=0.578). PCFS and KBILD improved similarly in the two groups. In individuals previously hospitalised for COVID-19, a 12-week supervised HIIT scheme resulted in a preserved LVM at 12-month follow-up but did not affect pulmonary diffusing capacity or symptom severity.

Frailty, Physical Function Impairment and Pulmonary Function in Aging Men with and without HIV from the Multicenter AIDS Cohort Study (MACS).

People aging with HIV (PAWH) experience greater impairment in physical and pulmonary function than individuals aging without HIV. We examined whether baseline physical function was associated with subsequent pulmonary impairments. Associations of frailty and physical function (gait speed [m/sec], grip strength [kg]) with pulmonary function (< 80% predicted diffusing capacity for carbon monoxide [DLCO] and forced expiratory volume [FEV1]) 3 years later were modeled; age, HIV status, and smoking were assessed as effect modifiers. Among1,024 men, (54% PAWH, 10% frail, 51% pre-frail), mean (SD) age = 53 (12) years, cumulative smoking = 12 (19) pack-years, gait speed = 1.1 (0.2) m/sec, and grip strength = 36.6 (9.2) kg. Frailty, pre-frailty, and weak grip strength were associated with higher odds of subsequent impaired DLCO and FEV1. Slow gait speed was associated with higher odds of DLCO impairment but not FEV1. No statistically significant modifications were found. Interventions to improve physical function may help preserve pulmonary function.

Chronic Airflow Limitation, Emphysema and Impaired Diffusing Capacity in Relation to Smoking Habits in a Swedish Middle-Aged Population.

Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity for carbon monoxide (DLCO) are present, but characteristics and symptoms vary with smoking exposure. To study the prevalence of CAL, emphysema and impaired DLCO in relation to smoking and respiratory symptoms in a middle-aged population. We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, DLCO, high-resolution computed tomography (HRCT) and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced expiratory volume (FEV1/FVC)<0.7. The overall prevalence was for CAL 8.8%, for impaired DLCO (DLCO<LLN) 5.7% and for emphysema 8.8%, with a higher prevalence in current smokers than in ex-smokers and never-smokers. The proportion of never-smokers among those with CAL, emphysema and impaired DLCO was 32%, 19% and 31% respectively. Regardless of smoking habits, the prevalence of respiratory symptoms was higher among people with CAL and impaired DLCO, compared to those with normal lung function. Asthma prevalence in never-smokers with CAL was 14%. In this group, asthma associated with lower FEV1 and more respiratory symptoms. In this large population-based study of middle-aged people, CAL and impaired DLCO were associated with common respiratory symptoms. Self-reported asthma was not associated with CAL in never-smokers. Our findings suggest that CAL in never-smokers signifies a separate clinical phenotype that may be monitored and, possibly, treated differently from smoking-related COPD. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Usefulness of serum transthyretin for prediction of the 1-year outcome in idiopathic pulmonary fibrosis: An evaluation of sarcopenic and nutritional indicators

BackgroundPatients with idiopathic pulmonary fibrosis (IPF) often experience sarcopenia and malnutrition. However, this has not been fully examined through longitudinal surveys. This study investigated whether sarcopenia and malnutrition were associated with 1-year outcomes in IPF. MethodsWe evaluated sarcopenia and nutritional status in 64 outpatients with IPF. We assessed the time-to-event for respiratory-related hospitalizations or deaths 12 months after enrollment. Sarcopenia was diagnosed by the criteria of the Asian Working Group for Sarcopenia, 2019. Nutritional status was assessed by serum transthyretin and the Geriatric Nutritional Risk Index (GNRI). ResultsThe average age was 73.6 ± 7.9 years, and the percent predicted forced vital capacity (FVC) was 81.9 ± 15.7%. Of the 64 patients, 24 (37.5%) had sarcopenia. The median serum transthyretin level and mean GNRI were 23.8 mg/dL and 102, respectively. Eleven patients (17.2%) experienced respiratory-related hospitalization or death within the first year. Cox regression analysis showed that the % predicted diffusion capacity for carbon monoxide, lowest oxygen saturation in the 6-min walk test, serum transthyretin level, and GNRI were significant predictors of 1-year outcomes. The Kaplan–Meier method, which divided the patients into two groups based on a transthyretin level of 22.6 mg/dL, showed a significant difference (P < 0.001, log-rank test). Sarcopenia and the percent predicted FVC did not predict the 1-year outcomes. ConclusionsThis pilot study represents the first longitudinal survey assessing patients with IPF for sarcopenia and malnutrition. Serum transthyretin levels may predict respiratory-related hospitalization or death within 1 year in patients with IPF.

Interferon-signaling pathways are upregulated in people with HIV with abnormal pulmonary diffusing capacity (DL CO ).

People with HIV (PWH) are at greater risk of developing lung diseases even when they are antiretroviral therapy (ART)-adherent and virally suppressed. The most common pulmonary function abnormality in PWH is that of impaired diffusing capacity of the lungs for carbon monoxide (DL CO ), which is an independent risk factor for increased mortality in PWH. Earlier work has identified several plasma biomarkers of inflammation and immune activation to be associated with decreased DL CO . However, the underpinning molecular mechanisms of HIV-associated impaired DL CO are largely unknown. Cross-sectional pilot study with PWH with normal DL CO (values greater than or equal to the lower limit of normal, DL CO ≥ LLN, N = 9) or abnormal DL CO (DL CO < LLN, N = 9). We compared the gene expression levels of over 900 inflammation and immune exhaustion genes in PBMCs from PWH with normal vs. abnormal DL CO using the NanoString technology. We found that 26 genes were differentially expressed in the impaired DL CO group. These genes belong to 4 categories: 1. Nine genes in inflammation and immune activation pathways, 2. seven upregulated genes that are direct targets of the interferon signaling pathway, 3. seven B-cell specific genes that are downregulated, and 4. three miscellaneous genes. These results were corroborated using the bioinformatics tools DAVID (Database for Annotation, Visualization and Integrated Discovery) and GSEA (Gene Sets Enrichment Analysis). The data provides preliminary evidence for the involvement of sustained interferon signaling as a molecular mechanism for impaired DL CO in PWH.

Pulmonary function in patients with idiopathic scoliosis 40 years after diagnosis

BACKGROUND CONTEXTPulmonary function in patients with scoliosis has been a topic of concern, with some reports of markedly decreased ventilatory function leading to disability and increased mortality in patients with severe scoliosis. Only limited data is available concerning pulmonary function in adult patients with scoliosis. PURPOSETo report the long-term pulmonary function (PF) in patients diagnosed with idiopathic scoliosis (IS) compared with an age-matched population using extended pulmonary function testing (EPFT). STUDY DESIGN/SETTINGRetrospective clinical follow-up. PATIENT SAMPLEA total of 177 patients seen at our institution from 1972 to 1983 for a pediatric spinal deformity were assessed for inclusion in the study. About 77/129 eligible patients with IS (60%) partook in a clinical examination including radiographs, and EPFT. OUTCOME MEASURESThe EPFT values included forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, vital capacity (VC), total lung capacity (TLC), residual volume (RV), RV/TLC ratio, diffusion capacity of carbon monoxide (DLco), carbon monoxide transfer coefficient (KCO) and alveolar volume (VA). Results were expressed with z-scores derived from height and arm span normative data. Z-scores were calculated as z-score=Measured PF-Predicted PF /Relative standard deviation (RSD). The limits of normal, are defined as the 5th and 95th percentile limits (z-score between −1.645 and 1.645), respectively. METHODSPatients underwent a clinical examination with full spine standing radiographs and EFPT. The results were compared between patients with thoracic and thoracolumbar/lumbar (TL/L) main curves, and overall compared with a background population. Results were expressed with z-scores derived from height and arm span normative data. RESULTSOf 77 included patients, 76 (99%) were females with a mean age of 54.6±2.5 years. The mean follow-up time was 40.8±2.8 years. Forty-four patients had thoracic main curves, and 33 had TL/L main curves. We found no pulmonary impairment based on z-scores in the total cohort or between groups, with only patients who were current or previous smokers, having z-scores below the normal limits Patients with main thoracic curves displayed significantly lower PF on mean absolute values and mean z-scores on FEV1, FVC, FEV1/FVC ratio, VC, TLC, and DLco compared with main TL/L curves. Patients with thoracic curves had significantly larger Cobb angles at follow-up; 52±17° compared with 40±22° (p-value <.05) in the TL/L group. We found no linear association between thoracic Cobb angle and degree of pulmonary impairment assessed with DLco, TLC, and FVC. Comparison of pulmonary z-scores based on arm span data, differed significantly on FVC and TLC, with the arm span measurements showing lower mean z-scores (p-value <.05). CONCLUSIONSUsing EPFT, no pulmonary impairment could be demonstrated compared to the age-matched population 40 years after a diagnosis of IS. However, patients with thoracic curves had decreased PF compared to patients with TL/L curves although within the normal range. Thus, when treated as current guidelines suggest, patients with idiopathic scoliosis can expect the same long-term pulmonary function as the general population.

Risk factors of mortality in patients with rheumatoid arthritis-associated interstitial lung disease: a single-centre prospective cohort study

ObjectivesTo determine the risk factors for mortality in Korean patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) in comparison to patients with RA but without ILD (RA-nonILD).MethodsData were extracted from a single-centre prospective cohort of RA patients with a chest computed tomography scan at an academic referral hospital in Korea. Patients with RA-ILD enroled between May 2017 and August 2022 were selected, and those without ILD were selected as comparators. The mortality rate was calculated, and the causes of each death were investigated. We used Cox proportional hazard regression with Firth’s penalised likelihood method to identify the risk factors for mortality in patients with RA-ILD.ResultsA total of 615 RA patients were included: 200 with ILD and 415 without ILD. In the RA-ILD group, there were 15 deaths over 540.1 person-years (PYs), resulting in mortality rate of 2.78/100 PYs. No deaths were reported in the RA-nonILD group during the 1669.9 PYs. The primary causes of death were infection (nine cases) and lung cancer (five cases), with only one death attributed to ILD aggravation. High RA activity (adjusted HR 1.87, CI 1.16–3.10), baseline diffusing capacity for carbon monoxide (DLCO) < 60% (adjusted HR 4.88, 95% CI 1.11–45.94), and usual interstitial pneumonia (UIP) pattern (adjusted HR 5.13, 95% CI 1.00–57.36) were identified as risk factors for mortality in RA-ILD patients.ConclusionPatients with RA-ILD have an elevated risk of mortality compared with those without ILD. Infection-related deaths are the main causes of mortality in this population. High RA activity, low DLCO, and the UIP pattern are significantly associated with the mortality in patients with RA-ILD.

Functional Improvement at One Year in Fibrotic Interstitial Lung Diseases-Prognostic Value of Baseline Biomarkers and Anti-Inflammatory Therapies.

The clinical spectrum of fibrotic interstitial lung diseases (ILDs) is highly heterogeneous. We aimed to evaluate the prognostic value of widely available baseline biomarkers for the improvement of lung function in patients with fibrotic ILDs. This registry-based study included 142 patients with fibrotic ILDs as defined by the presence of reticulation, traction bronchiectasis or honeycombing on initial high-resolution computed tomography (HRCT). Functional improvement at 1 year was defined as a relative increase of 5% in forced vital capacity (FVC) or of 10% in diffusion capacity for carbon monoxide (DLCO). The prognostic value of baseline biomarkers was evaluated for all patients and the subgroup with anti-inflammatory treatment. At one year, 44 patients showed improvement while 73 showed disease progression. Multivariate analyses found prognostic significance for age < 60 years (OR 5.4; 95%CI 1.9-15.4; p = 0.002), lactate dehydrogenase (LDH) >250 U/L (OR 2.5; 95%CI 1.1-5.8; p = 0.043) and blood monocyte count < 0.8 G/L (OR 3.5; 95%CI 1.1-11.3; p = 0.034). In 84 patients undergoing anti-inflammatory treatment, multivariate analysis revealed age < 60 years (OR 8.5 (95%CI 2.1-33.4; p = 0.002) as the only significant variable. Younger age, a higher LDH and lower blood monocyte count predicted functional improvement in fibrotic ILD patients, while in those treated with anti-inflammatory drugs, only age had significant implications.

Hypercapnia and lung function parameters in chronic obstructive pulmonary disease

BackgroundIn 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.MethodsThis 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].ResultsFVC% (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.ConclusionsRoutinely collected pulmonary function parameters, particularly FVC% and FEV1%, may predict chronic hypercapnia during COPD progression.