Impaired 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.

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.

Lung function at 1-year follow-up in patients with persistent dyspnea after mild COVID-19 – comparisons with moderate and critical COVID-19

Aim: To assess lung function in patients with persistent dyspnea 1 year after mild coronavirus disease 2019 (COVID-19) and compare with those hospitalized with moderate or critical COVID-19. Methods: Adults with confirmed severe acute respiratory syndrome coronavirus-2 infection with mild COVID-19 and persistent dyspnea (n = 18) or with moderate (n = 34) or critical COVID-19 (n = 19) were followed up 11–13 months after initial infection. Inclusion criteria were age &lt; 65 years, no smoking history, and no preexisting respiratory diseases. Sociodemographic and clinical data were collected, and patients underwent spirometry and measurement of diffusing capacity for carbon monoxide (DLCO). Results: The non-hospitalized patients were significantly younger and more often female compared with those in the moderate and critical groups (P = 0.002 and P &lt; 0.001, respectively). No significant differences in comorbidities or body mass index (BMI) were noted between severity groups. An obstructive spirometry pattern (ratio of forced expiratory volume during the first exhalation second to forced vital capacity under the lower limit of normal (LLN)) was found in 5.6, 5.9, and 5.3% of patients in the mild, moderate, and critical groups, respectively (P = 0.995). Abnormal DLCO (&lt; LLN) rates were seen in 5.6, 16.7, and 47.4% in the mild, moderate, and critical groups, respectively (P = 0.018). DLCO, expressed as a z-score, was significantly lower in the critical group compared with the mild group after adjustment for age, sex, and BMI. Conclusion: Only a few subjects with mild COVID-19 and persistent dyspnea had abnormal lung function 1 year after initial infection, assessed based on spirometry and DLCO measurements. An obstructive spirometry pattern at 1-year follow-up was uncommon even in patients with moderate or critical COVID-19. Impaired DLCO was more common in patients with critical COVID-19.

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/).

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.

Association between impaired diffusion capacity and small airway dysfunction: a cross-sectional study

BackgroundSmall airway dysfunction (SAD) and impaired diffusion capacity of the lungs for carbon monoxide (DLCO) are positively associated with a worse prognosis. Individuals with both dysfunctions have been identified in clinical, and it is unknown whether they had worse health status or need management. We conducted this study to explore the association between SAD and impaired DLCO, and the difference between the groups with two dysfunctions, with either one dysfunction, and with no dysfunction.MethodsThis study involved subjects partly from those who had returned for the third-year follow-up (up to December 2022) of the ECOPD Study and those who newly participated. We assessed the diffusion capacity, questionnaire, exacerbations, spirometry, impulse oscillometry (IOS), and computed tomography (CT). Impaired DLCOwas defined as DLCO%predicted &lt;80%. Spirometry-defined SAD was defined using MMEF %predicted, FEF50%predicted, and FEF75%predicted; at least two of the three being &lt;65% using post-bronchodilator spirometry. IOS-defined SAD was defined as R5-R20 &gt;0.07 kPa·L−1·s−1. CT-defined SAD was defined by LAA−856% comprising ≥15% of the total lung volume. Covariate analyses and logistic regression were performed to assess the association between impaired DLCOand SAD.ResultsThis study involved 581 subjects. The occurrence of both spirometry- and CT-defined SAD was significantly higher in subjects with impaired than normal DLCOSubjects with two dysfunctions were associated with worse preceding-year exacerbations than controls.ConclusionsImpaired diffusion capacity is positively associated with SAD. Subjects with impaired diffusion capacity and SAD may have a worse health status and need additional management.

Lung function and quality of life one year after severe COVID-19 in Brazil.

To evaluate symptoms, lung function, and quality of life of a cohort of patients hospitalized for severe COVID-19 12 months after hospital admission. This was a cross-sectional study. We included severe COVID-19 survivors hospitalized in one of three tertiary referral hospitals for COVID-19 in the city of Belo Horizonte, Brazil. Participants were submitted to lung function and six-minute walk tests and completed the EQ-5D-3L questionnaire. The whole sample comprised 189 COVID-19 survivors (mean age = 59.6 ± 13.4 years) who had been admitted to a ward only (n = 96; 50.8%) or to an ICU (n = 93; 49.2%). At 12 months of follow-up, 43% of patients presented with dyspnea, 27% of whom had a restrictive ventilatory disorder and 18% of whom presented with impaired DLCO. There were no significant differences in FVC, FEV1, and TLC between the survivors with or without dyspnea. However, those who still had dyspnea had significantly more impaired DLCO (14.9% vs. 22.4%; p < 0.020) and poorer quality of life. After one year, survivors of severe COVID-19 in a middle-income country still present with high symptom burden, restrictive ventilatory changes, and loss of quality of life. Ongoing follow-up is needed to characterize long COVID-19 and identify strategies to mitigate its consequences.

Phenotypes and outcome of diffuse pulmonary non-amyloid light chain deposition disease.

Light chain deposition disease (LCDD) is a very rare entity. Clinical manifestations of LCDD vary according to the organs involved. Data on pulmonary LCDD are scarce and limited to small series or case reports. This study aimed to describe the characteristics and outcome of diffuse pulmonary non-amyloid LCDD localized to the lungs. A multicenter retrospective cohort study was conducted. Clinical characteristics were collected, and chest CTs were centrally reviewed. The diagnosis of pulmonary non-amyloid LCDD was confirmed by immunohistochemistry. Thirty-one cases were identified (68% female), with a median age at diagnosis of 50 years (IQR 20). Baseline FEV1/FVC was < 0.70 in 45% of patients. Mean (± SD) FEV1 and DLCO were 86% ± 26.2 and 52% ± 23.9, respectively. CT revealed peculiar patterns of thin-walled cysts (58%) and thin-walled cystic bronchiectases (27%). Increased serum kappa light chain was found in 87% of patients. Histological analysis showed kappa light chain deposits in all patients, except one with lambda chain deposits. Median annual FEV1 decline was 127 ml (IQR 178) and median DLCO decline was 4.3% (IQR 4.3). Sixteen patients received immunomodulatory treatment or chemotherapy; serum light chain levels decreased in 9 cases (75%), without significant improvement in FEV1 (p = 0.173). Overall, 48% of patients underwent bilateral lung transplantation. Transplant-free survival at 5 and 10 years were 70% and 30%, respectively. An annual FEV1 decline greater than 127 ml/year was associated with increased risk of death or transplantation (p = 0.005). Diffuse pulmonary LCDD is characterised by female predominance, a peculiar imaging pattern with bronchiectasis and/or cysts, progressive airway obstruction and severe DLCO impairment, and poor outcome. Lung transplantation is a treatment of choice.

Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without Human Immunodeficiency Virus.

Rationale: Nocturnal hypoxemia is common in sleep-disordered breathing (SDB) and is associated with increased morbidity and mortality. Although impaired diffusing capacity of the lung for carbon monoxide (DlCO) is associated with daytime hypoxemia, its influence on SDB-related nocturnal hypoxemia is not known. Objectives: To characterize the effects of DlCO impairment on SDB-related nocturnal hypoxemia and associated health outcomes. Methods: Data from a multicenter cohort of men with and without human immunodeficiency virus (HIV) infection, with concomitant measures of DlCO and home-based polysomnography (n = 544), were analyzed. Multivariable quantile regression models characterized associations between DlCO and several measures of SDB-related hypoxemia (e.g., total sleep time with oxygen saturation as measured by pulse oximetry [SpO2] < 90% [T90]). Structural equation models were used to assess associations of impaired DlCO and SDB-related hypoxemia measures with prevalent hypertension and type 2 diabetes. Results: DlCO impairment (<80% predicted) was associated with sleep-related hypoxemia. Participants with severe SDB (apnea-hypopnea index ⩾ 30 events/h) and impaired DlCO had higher T90 (median difference, 15.0% [95% confidence interval (CI), 10.3% to 19.7%]) and average SDB-related desaturation (median difference, 1.0 [95% CI, 0.5 to 1.5]) and lower nadir SpO2 (median difference, -8.2% [95% CI, -11.4% to -4.9%]) and average SpO2 during sleep (median difference, -1.1% [95% CI, -2.1% to -0.01%]) than those with severe SDB and preserved DlCO. Higher T90 was associated with higher adjusted odds of prevalent hypertension (odds ratio, 1.39 [95% CI, 1.14 to 1.70]) and type 2 diabetes (odds ratio, 1.25 [95% CI, 1.07 to 1.46]). Conclusions: DlCO impairment in severe SDB was associated with sleep-related hypoxemia, prevalent hypertension, and type 2 diabetes. Assessment of SDB should be considered in those with impaired DlCO to guide testing and risk stratification strategies.

One-year follow-up of COVID-19 recoverees with impaired pulmonary function: A prospective cohort study

Decreased diffusion capacity for carbon monoxide (DLCO) is the most prevalent pulmonary testing abnormality among COVID-19 recoverees. We prospectively followed 51 individuals with impaired DLCO at an average of ∼3 months following COVID-19 and re-examined them at one year. At follow-up, mean DLCO increased from 68.0 % to 72.6 % (p = 0.002); while 33 % of the cohort experienced a clinically significant rise (>10 points) in DLCO, only 29 % normalized their values. While DLCO change did not correlate with symptoms, lack of improvement was more prevalent among individuals with obesity. Regardless of COVID-19 severity, a substantial proportion continued to exhibit DLCO impairment at 1-year.

A Medical Record-based Pilot Study on the Diffusing Capacity of the Lungs for Carbon Monoxide versus Nailfold Capillaroscopy as an Early Marker for Lung Involvement in Connective Tissue Disease-related Interstitial Lung Diseases

Abstract Background: Connective tissue disease (CTD)-related interstitial lung diseases (ILDs) are one of the most common ILDs which affect relatively younger populations and can lead to extensive lung damage and fibrosis. Early detection and initiation of anti-inflammatory therapy can curtail the extent of lung damage. The diffusing capacity of the lungs for carbon monoxide (DLCO) is a well-established early marker of ILD. While most of the studies have shown specific nailfold capillaroscopy (NFC) findings in patients with CTD-ILD, none of them has evaluated the relation between diffusion impairment and nailfold capillary changes. The present study was carried out to evaluate the relationship between DLCO and NFC as markers for lung involvement in CTD-ILDs. Materials and Methods: This was a medical record-based observational study wherein the medical records of 100 diagnosed patients of CTD-ILD attending the pulmonology and rheumatology outpatient department were screened. Data concerning NFC, spirometry, and DLCO were collected and analyzed. Results: In our study of 100 patients, the minimum age was 29 years, and the maximum age was 78 years. A majority of patients in the study were found to be males (58%) and were suffering from CTD-ILD for a duration ranging from 2 to 5 years (58%). Eighty-nine percentage had a functional impairment on spirometry in the form of reduced forced vital capacity, and 61% had impaired DLCO. Nailfold capillary abnormalities were observed in all but one patient. The most common abnormal finding was a loss of capillary density (95% of patients) and a decrease in the intercapillary distance (94% of patients). A significant correlation was seen between diffusion impairment and abnormal nailfold capillary length. However, there was no significant correlation between DLCO and overall nailfold capillary abnormalities. Conclusion: The study concludes that NFC cannot be used as a tool to monitor diffusion impairment of the lungs in CTD-ILD. DLCO is a better assessment method compared to NFC changes as an indicator of lung involvement in CTD-ILD.

Diffusing capacity as an independent predictor of acute exacerbations in chronic obstructive pulmonary disease

A weak correlation between diffusing capacity of the lung for carbon monoxide (DLCO) and emphysema has been reported. This study investigated whether impaired DLCO in chronic obstructive pulmonary disease (COPD) is associated with increased risk of acute exacerbation independent of the presence or extent of emphysema. This retrospective cohort study included patients with COPD between January 2004 and December 2019. The participants were divided into four groups based on visually detected emphysema and impaired DLCO. Among 597 patients with COPD, 8.5% had no emphysema and impaired DLCO whereas 36.3% had emphysema without impaired DLCO. Among the four groups, patients with impaired DLCO and emphysema showed a higher risk of moderate-to-severe or severe exacerbation than those with normal DLCO. Impaired DLCO was an independent risk factor for severe exacerbation (hazard ratio, 1.524 [95% confidence interval 1.121–2.072]), whereas the presence of emphysema was not. The risk of moderate-to-severe or severe exacerbation increases with the severity of impaired DLCO. After propensity-score matching for the extent of emphysema, impaired DLCO was significantly associated with a higher risk of moderate-to-severe (p = 0.041) or severe exacerbation (p = 0.020). In patients with COPD and heterogeneous parenchymal abnormalities, DLCO can be considered an independent biomarker of acute exacerbation.

Two-year diffusion capacity trajectory in COVID-19 pneumonia survivors.

Reduced diffusion capacity (DLCO) after COVID 19 pneumonia was reported in hospitalised patients after discharge. Here, we studied the restoration of DLCO over a 24months period in COVID-19 pneumonia survivors (n = 317), who were categorised into "moderate" cases (no oxygen supply; no need for hospitalisation), "severe" cases (respiratory frequency > 30/min and/or peripheral oxygen SpO2 < 93%), and "critical" cases (respiratory failure and admission into the intensive care unit). COVID-19 pneumonia survivors with a decreased DLCO (<80%) at 3months (n = 133) were invited for 6- and 24-months follow-up. At 3months, impairment of DLCO was more severe in critical case (p < .01). Over time, the subgroups showed a similar level of improvement; and, there was no difference in recovery over time between the subgroups. At 24months, the DLCO did not differ between the subgroups, with a mean DLCO of 73% for all patients. At 24months, 65% of patients still had a DLCO < 80%, and in 40% of patients DLCO was <70% of predicted. Regardless the initial disease severity, all COVID-19 survivors showed improvement in DLCO during follow-up; however, DLCO had not normalised in the majority of patients with a DLCO <80% 3months after hospital discharge.

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.

A comprehensive study to determine effect of coronavirus disease on pulmonary function of the affected patients

Background: As the global coronavirus disease-2019 (COVID-19) pandemic continues to unfold, understanding the implications of the disease on post-recovery lung function becomes crucial. This study aimed to investigate the early convalescent phase characteristics of lung function in patients recovering from COVID-19, shedding light on the extent and nature of lung impairments following acute infection. Aims and Objectives: This study aimed to investigate the early convalescent phase characteristics of lung function in patients recovering from COVID-19, shedding light on the extent and nature of lung impairments following acute infection. Materials and Methods: A cross-sectional analysis was conducted on 57 patients who had been diagnosed with COVID-19 and subsequently discharged from the hospital. Comprehensive lung function tests, chest computed tomography scans, and the 6-min walk test were performed approximately 30 days after discharge to assess pulmonary parameters, imaging abnormalities, and exercise tolerance. Results: The study revealed that more than half of the patients exhibited impairments in diffusing capacity (DLCO), respiratory muscle strength, and lung imaging abnormalities during the early convalescent phase. Notably, severe cases demonstrated a significantly higher incidence of DLCO impairment, accompanied by notable reductions in total lung capacity and 6-min walking distances compared to non-severe cases. Interestingly, the severity of illness or residual imaging changes did not consistently correlate with the observed lung function impairments. This observation challenges previous assumptions and underscores the complexity of the relationship between disease severity and post-recovery lung function. Conclusion: In the context of COVID-19 recovery, this study highlights the presence of early convalescent phase impairments in lung function, suggesting that the impact on respiratory health extends beyond the acute phase of infection.

Prognostic value of serum Krebs von den Lungen-6 (KL-6) levels in COVID-19 pneumonia

Background and objectivesKrebs von den Lungen-6 (KL-6), expressed by damaged type II pneumocytes, is useful in the diagnosis and severity assessment of many diffuse interstitial lung diseases. The objective of our study was to determine the prognostic value of the initial KL-6 plasma level in COVID-19 pneumonia. MethodsAll patients hospitalized for a suspected COVID-19 pneumonia between March and May 2020 in our Chest department of a French university hospital were included. KL-6 serum concentrations were measured within 72 h of diagnostic suspicion by chemiluminescence enzyme immunoassay Survival analysis was performed using a Cox regression and modeled by a Kaplan-Meier curve. ResultsSixty-six COVID-19 patients (average age = 64 ± 14 years, 71.2 % males) with KL-6 serum measurement were included. Median KL-6 serum concentration was 409 ± 312 U/mL. KL-6 was significantly higher in men (p = 0.003), elders (p = 0.0001) and in patients with greater Charlson's score (p = 0.002). Higher KL-6 concentration was significantly associated with in-hospital mortality (HR: 8.66; 95 % CI:1.1–69.2, p = 0.014), radiological extension of lesions on chest CT scan (p = 0.004) and higher WHO severity score (p = 0.042), but not with admission in intensive care unit. In 9 (14 %) non-surviving COVID-19 patients, KL-6 serum concentration increased whereas it remained stable or decreased in survivors. At 3 months follow-up (n = 48), DLCO was negatively correlated with the initial KL-6 value (r = 0.47, p = 0.001), while FVC, FEV1 and MRC score were not. ConclusionInitial KL-6 serum concentration is significantly associated with in-hospital mortality, unfavorable outcome, and persistent impairment of DLCO at 3 months. Initial KL-6 plasma determination appears as a prognostic biomarker in COVID-19 pneumonia.

Systemic Determinants of Exercise Intolerance in Patients With Fibrotic Interstitial Lung Disease and Severely Impaired DLCO.

The precise mechanisms driving poor exercise tolerance in patients with fibrotic interstitial lung diseases (fibrotic ILDs) showing a severe impairment in single-breath lung diffusing capacity for carbon monoxide (DLCO < 40% predicted) are not fully understood. Rather than only reflecting impaired O2 transfer, a severely impaired DLCO may signal deranged integrative physiologic adjustments to exercise that jointly increase the burden of exertional symptoms in fibrotic ILD. Sixty-seven subjects (46 with idiopathic pulmonary fibrosis, 24 showing DLCO < 40%) and 22 controls underwent pulmonary function tests and an incremental cardiopulmonary exercise test with serial measurements of operating lung volumes and 0-10 Borg dyspnea and leg discomfort scores. Subjects from the DLCO < 40% group showed lower spirometric values, more severe restriction, and lower alveolar volume and transfer coefficient compared to controls and participants with less impaired DLCO (P < .05). Peak work rate was ∼45% (vs controls) and ∼20% (vs DLCO > 40%) lower in the former group, being associated with lower (and flatter) O2 pulse, an earlier lactate (anaerobic) threshold, heightened submaximal ventilation, and lower SpO2 . Moreover, critically high inspiratory constrains were reached at lower exercise intensities in the DLCO < 40% group (P < .05). In association with the greatest leg discomfort scores, they reported the highest dyspnea scores at a given work rate. Between-group differences lessened or disappeared when dyspnea intensity was related to indexes of increased demand-capacity imbalance, that is, decreasing submaximal, dynamic ventilatory reserve, and inspiratory reserve volume/total lung capacity (P > .05). A severely reduced DLCO in fibrotic ILD signals multiple interconnected derangements (cardiovascular impairment, an early shift to anaerobic metabolism, excess ventilation, inspiratory constraints, and hypoxemia) that ultimately lead to limiting respiratory (dyspnea) and peripheral (leg discomfort) symptoms. DLCO < 40%, therefore, might help in clinical decision-making to indicate the patient with fibrotic ILD who might derive particular benefit from pharmacologic and non-pharmacologic interventions aimed at lessening these systemic abnormalities.

Health-Related Quality of Life Improves in Parallel with FEV1 and 6-Minute Walking Distance Test at Between 3 and 12 Months in Critical COVID-19 Survivors

BackgroundIn COVID-19 intensive care unit (ICU)–admitted patients, multiorgan acute complications lead to long-lasting sequelae. The aim of this study was to assess (1) changes in chest CT, pulmonary function test (PFT), functional capacity (6-minute walking distance test (6MWT)), and health-related quality of life (HR-QoL) among ICU COVID-19 survivors at 3, 6, and 12 months after ICU discharge and (2) predictors of persistent impairment/improvement in 6MWT and HR-QoL. MethodsICU COVID-19 survivors were prospectively included. Outcomes at 3, 6, and 12 months included PFT, 6MWT, respiratory muscle strength (RMS), HR-QoL (SF-36), Medical Research Council dyspnea scale (mMRC), and post-COVID Functional Status scale. ResultsEighty-seven survivors were included, from June 3, 2020, to September 2, 2021. At 12 months, 50% of PFT were normal, 46% were restrictive, and 22% showed reduced diffusing capacity for carbon monoxide (DLCO). Impaired DLCO was associated with ICU length of stay and age. In mixed linear model analysis, improvements in RMS and mMRC persisted over time regardless of the adjustments applied (P ≤ .050). SF-36 improved in parallel with FEV1 and 6MWT between 3 and 12 months (P ≤ .044), while increment in DLCO correlated with changes in FEV1 and total lung capacity (TLC) (p ≤ 0.026). ConclusionsThis longitudinal study demonstrated that improvements in SF-36 occur in parallel with improvements in FEV1 and 6MWT between 3 and 12 months post-ICU discharge in a sample of critically ill COVID-19 patients. However, PFT remained, however, abnormal in 50% of patients. Based on continued improvements observed from 3 to 12 months, it is anticipated that COVID-19 ICU patients will continue to recover similarly to ARDS patients.

VEGF-A plasma levels are associated with impaired DLCO and radiological sequelae in long COVID patients.

Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is characterized by persistent clinical symptoms following COVID-19. To correlate biomarkers of endothelial dysfunction with persistent clinical symptoms and pulmonary function defects at distance from COVID-19. Consecutive patients with long COVID-19 suspicion were enrolled. A panel of endothelial biomarkers was measured in each patient during clinical evaluation and pulmonary function test (PFT). The study included 137 PASC patients, mostly male (68%), with a median age of 55years. A total of 194 PFTs were performed between months 3 and 24 after an episode of SARS-CoV-2 infection. We compared biomarkers evaluated in PASC patients with 20 healthy volunteers (HVs) and acute hospitalized COVID-19 patients (n = 88). The study found that angiogenesis-related biomarkers and von Willebrand factor (VWF) levels were increased in PASC patients compared to HVs without increased inflammatory or platelet activation markers. Moreover, VEGF-A and VWF were associated with persistent lung CT scan lesions and impaired diffusing capacity of the lungs for carbon monoxide (DLCO) measurement. By employing a Cox proportional hazards model adjusted for age, sex, and body mass index, we further confirmed the accuracy of VEGF-A and VWF. Following adjustment, VEGF-A emerged as the most significant predictive factor associated with persistent lung CT scan lesions and impaired DLCO measurement. VEGF-A is a relevant predictive factor for DLCO impairment and radiological sequelae in PASC. Beyond being a biomarker, we hypothesize that the persistence of angiogenic disorders may contribute to long COVID symptoms.

Lymphangioleiomyomatosis: circulating levels of FGF23 and pulmonary diffusion.

Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM. This was a descriptive single-center study in which subjects with LAM and controls with unreported lung disease were recruited. Serum FGF23 levels were measured in all subjects. Clinical data, including pulmonary function testing, were retrospectively obtained from electronic medical records of LAM subjects. Associations between FGF23 levels and clinical features of LAM were explored via nonparametric hypothesis testing. The sample comprised 37 subjects with LAM and 16 controls. FGF23 levels were higher in the LAM group than in the control group. In the LAM group, FGF23 levels above the optimal cutoff point distinguished 33% of the subjects who had nondiagnostic VEGF-D levels. Lower FGF23 levels were associated with impaired DLCO (p = 0.04), particularly for those with isolated diffusion impairment with no other spirometric abnormalities (p = 0.04). Our results suggest that FGF23 is associated with pulmonary diffusion abnormalities in LAM patients and elicit novel mechanisms of LAM pathogenesis. FGF23 alone or in combination with other molecules needs to be validated as a biomarker of LAM activity in future clinical research.