Changes In Pulmonary Function Tests Research Articles

Wound healing rates in COPD patients undergoing traditional pulmonary rehabilitation versus tailored Wound-Centric interventions.

This comparative cross-sectional study, conducted at Shanghai Pulmonary Hospital, aimed to evaluate the efficacy of tailored wound-centric interventions (TWCI) versus traditional pulmonary rehabilitation (TPR) in enhancing wound healing in patients with chronic obstructive pulmonary disease (COPD). Enrolling 340 patients with confirmed COPD, the study randomly assigned participants to either the TWCI or TPR group for a 12-week programme. The primary outcome measured was the rate of wound healing, with secondary outcomes including changes in pulmonary function tests (PFTs) and quality of life (QoL) scores. The TWCI group received a customized programme integrating standard pulmonary rehabilitation with specific wound care strategies, such as enhanced oxygen therapy, nutritional supplementation, and infection control measures. In contrast, the TPR group underwent a conventional pulmonary rehabilitation programme without targeted wound care interventions. Wound healing rates, PFTs, and QoL scores were assessed at the end of the intervention and 3 months post-intervention. The TWCI group demonstrated a statistically significant improvement in wound healing rates compared with the TPR group. The TWCI group had a 15% higher rate of reduction in wound size, a 10% rise in complete healing rates, and a 20% drop in infection rates (p < 0.05). Specifically, TWCI group exhibited higher rates of wound size reduction, complete healing, and decreased infection rates. Additionally, long-term pulmonary function and overall quality of life improvements were more pronounced in the tailored group, underscoring the benefits of a personalized approach to managing COPD and wound care. The study concluded that integrating wound-specific care strategies with pulmonary rehabilitation significantly enhances health outcomes in COPD patients with wounds. These findings supported the adoption of customized, multidisciplinary care plans, suggesting that tailored interventions can offer a comprehensive solution to the complex needs of COPD patients, potentially redefining best practices in chronic disease management.

Understanding changes in pulmonary function and functional status in breast cancer patients after systemic chemotherapy and radiotherapy: a prospective study

BackgroundRespiratory complications in breast cancer (BC) patients after chemotherapy (CT) and radiotherapy (RT) have been well acquainted and these complications should be investigated to prevent secondary problems and/or improve BC patients’ clinical outcomes. Therefore, this study aimed to assess the potential acute effect of systemic chemotherapy and radiotherapy on respiratory function and functional status of patients with breast cancer.MethodsA total of 25 BC patients who were candidates for systemic chemotherapy and radiotherapy were recruited after oncological examination and included in this study. Respiratory function and functional status were assessed with the Pulmonary Function Test (PFT) and the Six-Minute Walk Test (6MWT), respectively. Patients were assessed before CT (c0), after CT (c1), and after RT (r1).Results25 BC patients were assessed in c0 and c1 while only 15 out of 25 patients (60%) were assessed in r1. The actual values of Forced vital capacity (FVC) (t = 2.338, p =.028), Forced expiratory volume in 1s (FEV1 (t = 2.708, p =.012), and the forced expiratory flow of between 25% and 75% of vital capacity (FEF25-75%) (t = 2.200, p =.038) were found significantly different after systemic CT. Inspiratory (MIP) and expiratory (MEP) muscle strength also did not show a significant change from c0 to c1. A significant effect of the type of surgery was found (Wilks’ lambda, F [1, 19] = 6.561, p =.019, ηp2 = 0.25) between c0 and c1 in actual FVC value. The main effect of time was found significant in FVC (F [2, 28] = 4.840, p =.016, ηp2 = 0.25) from c0 to r1. Pairwise comparisons with Bonferroni correction showed that there was a significant difference between c0 and r1 (p =.037).DiscussionThe present study showed decreased FVC and FEV1 actual values and percent predicted rates from baseline to the completion of treatment. Since the interactional effect of the type of surgery was significant, we suggest that clinical and demographic factors such as age should be considered when interpreting the early changes in PFT. In addition, the significant linear trend of decreasing in some specific outcomes in respiratory function also highlighted the need for continuous monitoring of potential respiratory problems in patients with BC from baseline to the completion of chemotherapy and radiotherapy.

A Phase 2 Randomized Clinical Trial Evaluating 4-Dimensional Computed Tomography Ventilation-Based Functional Lung Avoidance Radiation Therapy for Non-Small Cell Lung Cancer

PurposeTo determine whether 4-dimensional computed tomography (4DCT) ventilation-based functional lung avoidance radiotherapy preserves pulmonary function compared with standard radiotherapy for non-small cell lung cancer (NSCLC). Material and MethodsThis single center, randomized, phase 2 trial enrolled patients with NSCLC receiving curative intent radiotherapy with either stereotactic body radiotherapy or conventionally fractionated radiotherapy between 2016 and 2022. Patients were randomized 1:1 to standard of care radiotherapy or functional lung avoidance radiotherapy. The primary endpoint was the change in Jacobian-based ventilation as measured on 4DCT from baseline to three months post-radiation. Secondary endpoints included changes in volume of high- and low-ventilating lung, pulmonary toxicity, and changes in pulmonary function tests (PFTs). ResultsA total of 122 patients were randomized and 116 were available for analysis. Median follow up was 29.9 months. Functional avoidance plans significantly (P<.05) reduced dose to high-functioning lung without compromising target coverage or organs at risk constraints. When analyzing all patients, there was no difference in the amount of lung showing a reduction in ventilation from baseline to 3 months between the two arms (1.91% vs 1.87%; P=.90). Overall grade ≥2 and grade ≥3 pulmonary toxicities for all patients were 24.1% and 8.6%, respectively. There was no significant difference in pulmonary toxicity or changes in PFTs between the two study arms. In the conventionally fractionated cohort, there was a lower rate of grade ≥2 pneumonitis (8.2% vs 32.3%; P=.049) and less of a decline in change in FEV1 (-3 vs -5; P=.042) and FVC (1.5 vs -6; P=.005) at 3 months, favoring the functional avoidance arm. ConclusionsThere was no difference in post-treatment ventilation as measured by 4DCT between the arms. In the cohort of patients treated with conventionally fractionated radiotherapy with functional lung avoidance, there was reduced pulmonary toxicity, and less decline in PFTs suggesting a clinical benefit in patients with locally advanced NSCLC. Trial RegistrationClinicalTrials.gov Identifier: NCTXXXX Anonymized for Review XXXX

Early-life pulmonary viral infection leads to long-term functional and lower airway structural changes in the lungs.

Early-life respiratory virus infections have been correlated with enhanced development of childhood asthma. In particular, significant numbers of respiratory syncytial virus (RSV)-hospitalized infants go on to develop lung disease. It has been suggested that early-life viral infections may lead to altered lung development or repair that negatively impacts lung function later in life. Our data demonstrate that early-life RSV infection modifies lung structure, leading to decreased lung function. At 5 wk postneonatal RSV infection, significant defects are observed in baseline pulmonary function test (PFT) parameters consistent with decreased lung function as well as enlarged alveolar spaces. Lung function changes in the early-life RSV-infected group continue at 3 mo of age. The altered PFT and structural changes induced by early-life RSV were mitigated in TSLPR-/- mice that have previously been shown to have reduced immune cell accumulation associated with a persistent Th2 environment. Importantly, long-term effects were demonstrated using a secondary RSV infection 3 mo following the initial early-life RSV infection and led to significant additional defects in lung function, with severe mucus deposition within the airways, and consolidation of the alveolar spaces. These studies suggest that early-life respiratory viral infection leads to alterations in lung structure/repair that predispose to diminished lung function later in life.NEW & NOTEWORTHY These studies outline a novel finding that early-life respiratory virus infection can alter lung structure and function long-term. Importantly, the data also indicate that there are critical links between inflammatory responses and subsequent events that produce a more severe pathogenic response later in life. The findings provide additional data to support that early-life infections during lung development can alter the trajectory of airway function.

Pulmonary Function Tests Post-Stroke. Correlation between Lung Function, Severity of Stroke, and Improvement after Respiratory Muscle Training.

Stroke is a significant cause of mortality and chronic morbidity caused by cardiovascular disease. Respiratory muscles can be affected in stroke survivors, leading to stroke complications, such as respiratory infections. Respiratory function can be assessed using pulmonary function tests (PFTs). Data regarding PFTs in stroke survivors are limited. We reviewed the correlation between PFTs and stroke severity or degree of disability. Furthermore, we reviewed the PFT change in stroke patients undergoing a respiratory muscle training program. We searched PubMed until September 2023 using inclusion and exclusion criteria in order to identify studies reporting PFTs post-stroke and their change after a respiratory muscle training program. Outcomes included lung function parameters (FEV1, FVC, PEF, MIP and MEP) were measured in acute or chronic stroke survivors. We identified 22 studies of stroke patients, who had undergone PFTs and 24 randomised controlled trials in stroke patients having PFTs after respiratory muscle training. The number of patients included was limited and studies were characterised by great heterogeneity regarding the studied population and the applied intervention. In general, PFTs were significantly reduced compared to healthy controls and predicted normal values and associated with stroke severity. Furthermore, we found that respiratory muscle training was associated with significant improvement in various PFT parameters and functional stroke parameters. PFTs are associated with stroke severity and are improved after respiratory muscle training.

Changes in pulmonary function tests after needle versus laser acupoint stimulation

Changes in pulmonary function tests after needle versus laser acupoint stimulation

Efficacy of N-acetylcysteine plus pirfenidone in the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis

BackgroundNumerous studies have demonstrated the potential of pirfenidone to enhance the prognosis of patients afflicted with idiopathic pulmonary fibrosis (IPF). Although N-acetylcysteine (NAC) is utilized as an antioxidant in IPF treatment, the combination of NAC and pirfenidone has produced inconsistent outcomes in certain studies. To assess the clinical effectiveness and safety of NAC plus pirfenidone (designated as the treatment group) versus pirfenidone monotherapy (designated as the control group), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs).MethodsRCTs of NAC plus pirfenidone were reviewed searching from databases and networks of unpublished and published studies in any language. Using pair-wise meta-analysis, changes in pulmonary function test (PFT) parameters and safety were evaluated.ResultsTwo independent reviewers selected and obtained data from 5 RCTs (n = 398), comprising 1 study from Japan, 1 from Europe, and 3 from China. NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of skin effects(RR 1.26 [95%CI 0.64 to 2.45]) and mortality(RR 0.35 [95%CI 0.07 to 1.68])(both moderate certainty). NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of at least one side effects(RR 1.00 [95%CI 0.84 to 1.19]; low certainty),severe side effects(RR 0.67 [95%CI 0.30 to 1.47]; low certainty) and gastrointestinal effects(RR 0.67 [95%CI 0.41 to 1.09]; low certainty) with possibly no effect in Δ%DLco(SMD -0.17 [95%CI -0.15 to 0.48]; low certainty). Meanwhile, the effect of NAS plus pirfenidone as compared to pirfenidone monotherapy on ΔFVC(SMD 0.18 [95%CI -0.68 to 1.05]), Δ%FVC(SMD -2.62 [95%CI -5.82 to 0.59]) and Δ6MWT(SMD -0.35 [95%CI -0.98 to 0.28]) is uncertain(extremely low certainty).ConclusionModerate certainty evidence suggests that NAS plus pirfenidone, compared to pirfenidone monotherapy for IPF, does not reduce the incidence of skin effects and mortality.

Comparative study of pulmonary functions test among different substances abusers

BackgroundSubstance use is a problem that affects people all over the world and is prevalent in different age groups. The lungs in particular, with their unique exposure to the environment and the bloodstream, are vulnerable to damage from substance use and can affect lung function. Efforts have generally focused on cigarettes, while there is little research on different substances of use. The study aimed to detect changes in pulmonary function tests in different substance users.MethodsAn analytical cross-sectional study was carried out among different substance users at the Abdalaal Elidridi Psychiatric Hospital. A total of 60 adults were included: 16 cannabis users, 16 heroin users, 16 methamphetamine users, and 12 alcohol users. Participants used only one substance. Height and weight were measured, and BMI was calculated. For each participant, pulmonary function tests (PFTs) including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC ratio and peak expiratory flow rate (PEFR) were measured using an electronic spirometer, and the results were compared with normal reference values for Sudanese subjects matched for age, sex, and height.ResultsA high prevalence of lung function abnormalities (100.0%) is seen in all abusers. Obstructive lung disease is found in 80.0% of patients, and restrictive lung disease is found in 20.0% of cases. The measured FEV1/FVC ratio in different substance groups was lower than the expected normal values of (88.2 ± 2.9%). The mean FEV1/FVC ratio of alcohol was (83.6 ± 7.6%), for heroin, it was (77.3 ± 15.8%), for methamphetamine, it was (77.7 ± 17.8%) and for cannabis, it was (71.03 ± 11.3%), the latter was significantly lower than the other two groups (P < 0.001). Duration of substance use was inversely correlated with the FEV1/FVC ratio (r = -0.378, P 0.001), indicating that a longer duration of substance use correlates with lower FEV1/FVC ratios.ConclusionsObstructive lung abnormalities are frequent in substance abusers. All types of substances have a major deleterious effect on PFTs and harm the respiratory system. More action should be taken to address the effects of substances on the lungs. Awareness, early detection, and intervention are essential.

Impact on Pulmonary Function in a Randomized Trial of Single-Fraction and Multifraction Stereotactic Body Radiation Therapy for Pulmonary Oligometastatic Disease: An Analysis of TROG 13.01 (SAFRON II)

Background[Anonymized] was a phase 2 multicentre trial comparing single fraction and multi-fraction SBRT. Patients with 1-3 peripheral pulmonary oligometastases were randomized 1:1 between 28Gy in 1 fraction and 48Gy in 4 fractions. There were no differences between arms in efficacy or toxicity. We performed an analysis to assess changes in pulmonary function tests (PFTs) between arms over time and assessed the impact of the number and total volume of targets on PFT change over time. MethodsA linear mixed model was used to describe the PFTs by treatment arm over time. The effect of number and volume of targets on PFTs at 6 and 12 months was assessed by a simple linear model. ResultsNinety patients were randomised; 87 were treated for 133 pulmonary oligometastases. Forty-four were randomised to the SF arm and 43 to the MF arm. There were no differences in absolute or relative PFT measures of forced expiratory volume in 1 second (FEV1),diffusing capacity of the lungs for carbon monoxide (DLCO) or Forced Vital Capacity (FVC) between the two arms. At 12 months, there was a reduction in absolute DLCO from baseline (−1.7ml/min/mmHg, [95%CI: −2.5; −1.0]), relative DLCO (−5.5% [−8.4;-2.6]),absolute FEV1 (−0.17L [−0.23;-0.11]) and absolute FVC (-0.20L [−0.27;-0.13]). In patients with multiple pulmonary targets, increase in target number (per lesion) was associated with a reduction in the absolute FEV1 at 6 months of −0.10L [−0.18; −0.03] (p = 0.007),FEV1 at 12 months −0.10L [−0.20; −0.01] (p = 0.04), FVC at 6 months of −0.11L [−0.20; −0.03] (p = 0.014), FVC at 24 months −0.13L [−0.25; −0.01] (p = 0.036) Reduction in FEV1 was also seen per 10ml increase in PTV at 12 months −0.03L [−0.06; −0.00] (p = 0.036). Number of targets and PTV were not associated with DLCO. ConclusionTreating multiple targets resulted in increased loss of FEV1 and FVC but not DLCO. There were no significant differences in PFT decline between SF and MF SBRT.

Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD): Primary Analysis of a Phase II Trial

The use of stereotactic ablative radiotherapy (SABR) in patients with fibrotic interstitial lung disease (ILD) has been associated with an increased risk of toxicity, but patients with ILD and lung cancer may have no other options for curative-intent treatment. The goal of the ASPIRE-ILD trial was to assess the benefits and toxicities of SABR in patients with fibrotic ILD. We enrolled patients with fibrotic ILD and a diagnosis of T1-2N0 NSCLC who were not candidates for surgery. All patients were centrally reviewed prior to enrollment to confirm the presence and subtype of ILD. After stratification by the ILD-GAP score (a measure of ILD severity and prognosis), patients were treated with SABR to a dose of 50 Gy in 5 fractions EOD (BED = 100 Gy10), with a built-in de-escalation protocol in case of unacceptable toxicity. The primary endpoint was overall survival (OS), powered to distinguish 1-year OS >70% vs. an unacceptable rate of ≤50%. Secondary endpoints included toxicity (CTC-AE version 4.0), progression-free survival (PFS), local control (LC), patient-reported outcomes (FACT-L quality of life and cough severity), and changes in pulmonary function tests (PFTs). The study pre-specified that SABR would be considered worthwhile if median OS was >1 year, with a grade 3-4 toxicity risk <35% and a grade 5 toxicity risk <15%. Target accrual was 39 treated patients. Thirty-nine patients were enrolled and treated with SABR between March 2019 and January 2022, all to a dose of 50 Gy in 5 fractions, at 5 institutions in Canada and 1 in Scotland. Median age was 78 years (interquartile range: 67-83), 59% were male, and 92% had a history of smoking (median 43 pack-years). At baseline, 70% reported dyspnea, median FEV1 was 80% predicted and median DLCO was 49% predicted. ILD-GAP scores were as follows: ≤2 (i.e., best ILD status): n = 14; 3-5: n = 23; ≥6 (i.e., worst ILD status): n = 2. Median follow-up was 19 months. OS at 1-year was 78.9% (p<0.001 by binomial test vs. the unacceptable rate). Median OS was 25 months, median PFS was 19 months, and 2-year LC was 92%. AE rates (possibly, probably or definitely related) were as follows (highest grade per patient): grade 1-2: n = 12 (31%); grade 3: n = 4 (10%); grade 4; n = 0; grade 5 n = 3 (7.7%, all due to respiratory deterioration). AE rates did not differ by ILD-GAP category or ILD subtype. FACT-L scores trended downward over time (p = 0.07), and cough severity scale scores worsened over time (p = 0.02). Comparing last-available PFTs with baseline, DLCO declined (median: -4%; p = 0.046), FVC trended downward (median: -2.5%; p = 0.11), and FEV1 remained stable (median change: 0%). The use of SABR in patients with ILD met the pre-specified acceptability thresholds for both toxicity and efficacy, supporting the use of SABR for curative-intent treatment after a careful discussion of risks and benefits. Further studies exploring pharmacologic options to reduce toxicity may be beneficial in this population. ().

Could Poor Outcomes for Patients with Limited Lung Function Treated with SAbR Necessitate PULSAR?

Stereotactic ablative radiotherapy (SAbR) employs precise targeting and delivery of ablative radiation doses in patients with medically inoperable early-stage non-small cell lung cancer, as well as patients with pulmonary metastases. SAbR is well tolerated with few studies reporting a minimal decline in pulmonary function tests (PFTs). However, poor pulmonary function is considered a risk factor for radiation induced lung toxicity. Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) is an adaptive radiation therapy regimen where radiation pulses are delivered over longer periods of time, thereby allowing for modification of the treatment based on the patient's response, as well as limiting toxicities. As such, we hypothesize that treating patients with poor pulmonary function using a PULSAR approach is better tolerated in when compared to patients treated with SAbR. We performed a retrospective review of our institutional database of patients treated with SAbR to lung lesions from 2005 to 2022. We assessed the overall survival in stage-matched patients with normal vs poor lung function who received SAbR (40 patients in each cohort). Patients with decreased lung function included those with a diagnosis of moderate/severe COPD, restrictive lung disease, or patients needing home oxygen at the time of treatment. We then analyzed PFTs changes for patients receiving SAbR, and evaluated these changes relative to treatment delivery. Stage-matched Kaplan-Meier analysis of patients with normal vs poor lung function receiving SAbR revealed a statistically significant difference in survival with Log-rank test p = 0.007. Of the patients with PFTs, 45 (90%) received SAbR with two to three treatments weekly, while 5 (10%) were treated on a PULSAR regimen with one fraction every week to three weeks. No trends or significant differences are observed in the changes of total lung capacity (TLC), the first second of exhalation (FEV1), forced vital capacity (FVC) or FEV1/FVC ratios. However, we did note variations in the diffusing capacity of the lung for carbon monoxide (DLCO). The mean difference in DLCO for the SAbR and PULSAR groups were -26.07% (95% CI: -31.28 to -20.87, p < 0.0001), and -10.52% (95% CI: -40.74 to 19.69, p = 0.388), respectively. We observed a significant difference in overall survival between patients with normal vs poor lung function receiving SAbR. In a preliminary analysis, we discovered a small decline in DLCO for patients treated with regularly scheduled SAbR treatments. In the patients treated on the PULSAR regimen, however, this change in DLCO is not statistically significant. While this data suggests that increasing the time frame between individual doses of radiation may result in better toleration of radiotherapy in this patient population, the sample size of patients treated via PULSAR is limited, and longer follow-up is needed to further evaluate the potential benefits.

Angiotensin-converting enzyme 1 gene polymorphisms in patients with systemic sclerosis-associated interstitial lung disease: a single centre retrospective observational study.

Angiotensin-converting enzyme (ACE) 1 gene polymorphisms have been associated with vascular permeability, alveolar endothelial dysfunction and fibroblast proliferation and have been studied in pulmonary diseases such as COPD and idiopathic pulmonary fibrosis. Similar mechanisms of ACE 1 polymorphisms have been seen in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). We are presenting a retrospective observational study in patients with SSc-ILD and analysing the association of ACE 1 gene polymorphisms (DD, II and ID) with the features of SSc, changes in pulmonary function tests (PFTs) and lung HRCT over three different periods of time (at the time of the diagnosis, 5 and 10years after the diagnosis). The aim of the study was to determine whether ACE 1 gene polymorphisms have an effect on the severity of SSc-ILD. We found no statistically significant differences in the development and severity of SSc-ILD and changes in PFTs between subgroups of ACE 1 gene polymorphism over the analysed periods (at the time of diagnosis HRCT changes p = 0.270, FEV1 p = 0.483, FVC p = 0.497, DLco p = 0.807, after 5years HRCT changes p = 0.163, FEV1 p = 0.551, FVC p = 0.362, DLco p = 0.620 and 10years of follow-up HRCT changes p = 0.853, FEV1 p = 0.589, FVC p = 0.328, DLco p = 0.992). However, patients with the ID genotype showed a significant reduction in FEV1 after 10years of follow-up in comparison to baseline levels (91.0 (IR 80.0-105.0) at the time of diagnosis and 84.0 (IR 69.0-99.0) after 10years, p = 0.014). Our study suggests that ACE 1 gene polymorphisms do not have a role in the severity of SSc-ILD. Further studies are needed to explain the exact role of ACE 1 gene polymorphisms in SSc-ILD and SSc in general.

Assessment of a close respiratory follow-up schedule at 3 and 6 months after acute COVID-19 and its related investigations

BackgroundRespiratory sequela after acute COVID-19 is common and requires medical follow-up. Considering its vast economic impact, there is still no consensus regarding the mid-term follow-up plan after recovery. ObjectiveTo evaluate the necessity of a close pulmonary follow-up schedule after acute COVID-19 and its related investigations. MethodsA prospective cohort study including adult patients after acute COVID-19 pneumonia. Patients were invited or referred to a 3- and 6-month follow-up visits at a large pulmonary institute in a tertiary center. Before each visit, patients completed demographic and clinical questionnaires, pulmonary function tests (PFTs), and chest CT scans. Results168 patients were included after completing both visits (medians of 80 and 177 days). Their mean age was 58 ± 15 and 52% recovered from severe or critical COVID-19. Between the two visits, there was no change in DLCOc (mean 73 ± 18 %predicted in both visits) and FVC (mean 90 ± 16 vs. 89 ± 16 %predicted). The COPD assessment tool and modified Medical Research Council scale had inverse correlations with the DLCOc, and similarly did not change between the visits. Occupational exposures were the only factor associated with a change in DLCOc during follow-up (3% decrease, p = 0.04). An improvement in chest CT findings at the second visit was not associated with a change in PFTs. ConclusionsMost clinical variables did not change during a close follow-up schedule in the first six months after acute COVID-19. Such a follow-up plan does not appear necessary and should be personalized to limit excessive costs and resources.

A double-blind, placebo-controlled, randomized withdrawal trial of sarilumab for the treatment of glucocorticoid-dependent sarcoidosis.

Effective steroid-sparing therapies for the treatment of sarcoidosis are lacking; IL-6 antagonists may reduce sarcoidosis disease activity. This study assessed the safety and efficacy of the IL-6 receptor antagonist, sarilumab, in subjects with glucocorticoid-dependent sarcoidosis. This phase II, double-blind, placebo-controlled, randomized withdrawal trial enrolled 15 subjects with biopsy-proven sarcoidosis at Stanford University from November 2019 to September 2022. In period 1, subjects were treated with open-label s.c. sarilumab 200 mg every 2 weeks for 16 weeks, with predefined tapering of prednisone. Subjects who completed period 1 without a sarcoidosis flare entered period 2 and were randomized to continue sarilumab or to receive matching placebo for 12 weeks. The end points included flare-free survival, as well as changes in pulmonary function tests, chest imaging, patient-reported outcomes, and laboratory values. Fifteen subjects were enrolled in the study (median age 57 years, 80% male, 73.3% White), and 10 subjects successfully completed period 1. During period 1, 4 of the 15 subjects (26.7%) discontinued due to worsening of their sarcoidosis, and CT chest imaging worsened in 5 of the 15 subjects (35.7%). During period 2, 0 of 2 subjects in the sarilumab group and 1 of 8 subjects (12.5%) in the placebo group had a flare. Treatment with sarilumab 200 mg was generally well tolerated in subjects with sarcoidosis. In this double-blind, placebo-controlled, randomized withdrawal trial, a meaningful signal of improvement in subjects with sarcoidosis treated with sarilumab was not observed. Given the small numbers in this study, no definitive conclusions can be drawn. ClinicalTrials.gov, http://clinicaltrials.gov, NCT04008069.

Hyperpolarised xenon-129 diffusion-weighted magnetic resonance imaging for assessing lung microstructure in idiopathic pulmonary fibrosis.

Hyperpolarised 129-xenon (129Xe) magnetic resonance imaging (MRI) shows promise in monitoring the progression of idiopathic pulmonary fibrosis (IPF) due to the lack of ionising radiation and the ability to quantify functional impairment. Diffusion-weighted (DW)-MRI with hyperpolarised gases can provide information about lung microstructure. The aims were to compare 129Xe DW-MRI measurements with pulmonary function tests (PFTs), and to assess whether they can detect early signs of disease progression in patients with newly diagnosed IPF. This is a prospective, single-centre, observational imaging study of patients presenting with IPF to Northern General Hospital (Sheffield, UK). Hyperpolarised 129Xe DW-MRI was performed at 1.5 T on a whole-body General Electric HDx scanner and PFTs were performed on the same day as the MRI scan. There was an increase in global 129Xe apparent diffusion coefficient (ADC) between the baseline and 12-month visits (mean 0.043 cm2·s-1, 95% CI 0.040-0.047 cm2·s-1 versus mean 0.045 cm2·s-1, 95% CI 0.040-0.049 cm2·s-1; p=0.044; n=20), with no significant change in PFTs over the same time period. There was also an increase in 129Xe ADC in the lower zone (p=0.027), and an increase in 129Xe mean acinar dimension in the lower zone (p=0.033) between the baseline and 12-month visits. 129Xe DW-MRI measurements correlated strongly with diffusing capacity of the lung for carbon monoxide (% predicted), transfer coefficient of the lung for carbon monoxide (KCO) and KCO (% predicted). 129Xe DW-MRI measurements appear to be sensitive to early changes of microstructural disease that are consistent with progression in IPF at 12 months. As new drug treatments are developed, the ability to quantify subtle changes using 129Xe DW-MRI could be particularly valuable.

Diagnostic finding on high-resolution computed tomography (HRCT) predicts a good response to pirfenidone in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a debilitating condition, with a life expectancy of 2 to 5 years after diagnosis. Pirfenidone is a drug that has been shown to reduce the decline in forced vital capacity (FVC). We sought to identify whether different patterns on high-resolution computed tomography (HRCT) have different clinical effects through a retrospective comparison of baseline values and changes in pulmonary function tests (PFTs) after treatment with pirfenidone. We retrospectively analyzed data from IPF patients treated with pirfenidone at Nanjing Drum Tower Hospital in Jiangsu Province, China. According to the HRCT pattern, the patients were divided into usual interstitial pneumonitis (UIP) and possible UIP groups. Baseline clinical characteristics and changes every 6 months in the PFTs during the follow-up period were compared between the 2 groups. A total of 65 consecutive patients were enrolled. According to the HRCT pattern, patients were clustered into the UIP group (n = 46) and possible UIP group (n = 19). No difference was observed in the baseline PFTs ratio between the 2 groups. The FVC values of the 2 groups were not significantly different at the initial treatment and at 6 and 12 months after pirfenidone treatment (P = .081, 0.099, and 0.236, respectively). The improvement in % diffusion capacity of the lung for carbon monoxide (%DLCO) was higher in the possible UIP group after 6 and 12 months of pirfenidone treatment (P = .149, 0.026, and 0.025, respectively). The annual decrease in FVC was not significantly different between the 2 groups, and the annual decrease in %DLCO in the UIP group was significantly higher than that in patients with the possible UIP type (-7.767 ± 12.797 vs 0.342 ± 20.358, P < .05). These results indicate that patients with IPF with a possible UIP pattern on HRCT showed indications of a good response to pirfenidone.

Change in pulmonary function tests and their relation to the serum levels of ceruloplasmin, copper and superoxide dismutase in patients suffering from Type-1 and Type-2 diabetes.

To correlate the serum levels of ceruloplasmin (Cp), copper (Cu), and superoxide dismutase (SOD) with pulmonary function tests (PFTs) in non-diabetics (controls) and patients suffering from Type-1 and Type- 2 diabetes. The comparative cross-sectional study of 348 participants was performed at the Baqai Institute of Diabetes and Endocrinology (BIDE) - Karachi, Pakistan, from February 2019 to September 2020. Individuals having diabetes-related complications, asthma, chronic obstructive pulmonary disease, chest infection, pregnant women and smokers were excluded. A total of 348 participants were included into three groups after signing informed consent. The control group had 107 non-diabetic participants, with an age range of 6 to 60 years. The diagnosed T1D group (n=107) had an age range of 6 to 25 years. While diagnosed T2D group (n=134) had an age range of 26 to 60 years. During the fasting state, anthropometric parameters, blood pressure, spirometry, and a venous blood sample (5ml) were collected to measure serum Cp, serum Cu, serum SOD, and HbA1c levels by using commercially available kits. The SPSS, version 21, was used for data analysis. The reduced FVC (p-value <0.001), FEV1 (p-value <0.001), and PEFR (p-value <0.001) were found in both groups of diabetes. However, the lower levels of serum Cu (p-value <0.001), SOD (p-value <0.001), and significantly increased values of FEV1/ FVC (p-value <0.001) and Cp levels (p-value 0.030) were found only in T2D group as compared to T1D and controls. The study found no significant correlation of PFTs and serum Cp, Cu, and SOD levels in patients suffering from T1D and T2D. Hyperglycemia leads to more non-enzymatic glycosylation of tissue proteins that reflects reduced PFTs and increased Cp; particularly in T2D, which may alter lung tissue's physiology. Moreover, the study showed no correlation of PFTs with the Cp, Cu, and SOD in patients suffering from T1D and T2D.

Dynamic Prediction of Pulmonary Hypertension in Systemic Sclerosis Using Landmark Analysis.

Pulmonary hypertension (PH) is a serious complication of systemic sclerosis (SSc). In this study, we explored the prediction of short-term risk for PH using serial pulmonary function tests (PFTs) and other disease features. SSc patients in whom disease onset occurred ≥10 years prior to data retrieval and for whom autoantibody specificity and PFT data were available were included in this study. Mixed-effects modeling was used to describe changes in PFTs over time. Landmarking was utilized to include serial assessments and stratified Cox proportional hazards regression analysis with landmarks as strata was used to develop the PH prediction models. We analyzed data from 1,247 SSc patients, 16.3% of whom were male and 35.8% of whom had diffuse cutaneous SSc. Anticentromere, antitopoisomerase, and anti-RNA polymerase antibodies were observed in 29.8%, 22.0%, and 11.4% of patients, respectively, and PH developed in 13.6% of patients. Over time, diffusing capacity for carbon monoxide (DLco) and carbon monoxide transfer coefficient (Kco) declined in all SSc patients (up to 1.5% per year) but demonstrated much greater annual decline (up to 4.5% and 4.8%, respectively) in the 5-7 years preceding PH diagnosis. Comparisons between multivariable models including either DLco, Kco, or forced vital capacity (FVC)/DLco ratio, demonstrated that both absolute values and change over the preceding year in those measurements were strongly associated with the risk of PH (hazard ratio [HR] 0.93 and 0.76 for Kco and its change; HR 0.90 and 0.96 for DLco and its change; and HR 1.08 and 2.01 for FVC/DLco ratio and its change; P < 0.001 for all). The Kco-based model had the greatest discriminating ability (Harrell's C-statistic 0.903). Our findings strongly support the importance of PFT trends over time in identifying patients at risk of developing PH.

Expert consensus on the management of systemic sclerosis-associated interstitial lung disease

BackgroundSystemic sclerosis (SSc) is a rare, complex, connective tissue disorder. Interstitial lung disease (ILD) is common in SSc, occurring in 35–52% of patients and accounting for 20–40% of mortality. Evolution of therapeutic options has resulted in a lack of consensus on how to manage this condition. This Delphi study was initiated to develop consensus recommendations based on expert physician insights regarding screening, progression, treatment criteria, monitoring of response, and the role of recent therapeutic advances with antifibrotics and immunosuppressants in patients with SSc-ILD.MethodsA modified Delphi process was completed by pulmonologists (n = 13) and rheumatologists (n = 12) with expertise in the management of patients with SSc-ILD. Panelists rated their agreement with each statement on a Likert scale from − 5 (complete disagreement) to + 5 (complete agreement). Consensus was predefined as a mean Likert scale score of ≤ − 2.5 or ≥ + 2.5 with a standard deviation not crossing zero.ResultsPanelists recommended that all patients with SSc be screened for ILD by chest auscultation, spirometry with diffusing capacity of the lungs for carbon monoxide, high-resolution computed tomography (HRCT), and/or autoantibody testing. Treatment decisions were influenced by baseline and changes in pulmonary function tests, extent of ILD on HRCT, duration and degree of dyspnea, presence of pulmonary hypertension, and potential contribution of reflux. Treatment success was defined as stabilization or improvement of signs or symptoms of ILD and functional status. Mycophenolate mofetil was identified as the initial treatment of choice. Experts considered nintedanib a therapeutic option in patients with progressive fibrotic ILD despite immunosuppressive therapy or patients contraindicated/unable to tolerate immunotherapy. Concomitant use of nintedanib with MMF/cyclophosphamide can be considered in patients with advanced disease at initial presentation, aggressive ILD, or significant disease progression. Although limited consensus was achieved on the use of tocilizumab, the experts considered it a therapeutic option for patients with early SSc and ILD with elevated acute-phase reactants.ConclusionsThis modified Delphi study generated consensus recommendations for management of patients with SSc-ILD in a real-world setting. Findings from this study provide a management algorithm that will be helpful for treating patients with SSc-ILD and addresses a significant unmet need.

A comparative study of efficacy and safety of montelukast versus acebrophylline as add-on therapy to inhaled corticosteroids in bronchial asthma

Background: Non-responding to standard doses of inhalational corticosteroids (ICS) remains a challenge in the management of asthma, requiring add-on therapy. Acebrophylline, a theophylline derivative, with multiple mechanisms of action and properties, could work as a suitable alternative to montelukast as an add-on therapy. Aims and Objectives: The aim of this study was to compare the efficacy and safety of montelukast versus acebrophylline as an add-on therapy to ICS in the treatment of bronchial asthma. Materials and Methods: One hundred bronchial asthma patients, fulfilling inclusion/exclusion criteria, were enrolled and randomized in a 1:1 ratio into two groups of 50 each to receive either oral montelukast 10 mg OD or oral acebrophylline 200 mg OD with budesonide. Inhaled salbutamol was permitted as rescue medication during acute exacerbations. Primary outcome measures were change in pulmonary function test (PFT) parameters and asthma control questionnaire (ACQ) scores at baseline and 12 weeks. Adverse events, if any were recorded. Results: There was a statistically significant difference in the improvement of mean PFT parameters at the end of 12 weeks in the montelukast group (P &lt; 0.001), but not in acebrophylline group (P = 0.253). Montelukast was more efficacious than acebrophylline in improving PFT parameters at 6 and 12 weeks. Both treatment modalities significantly improved ACQ score at 12 weeks (P &lt; 0.001), the difference between two groups was not statistically significant (1.4 ± 0.53 in Group A vs. 1.32 ± 0.44 in Group B, P = 0.436). No significant adverse effects were seen in both groups. Conclusion: Montelukast, with low-dose ICS, had better efficacy over acebrophylline. Both montelukast and acebrophylline improved the quality of life in mild-to-moderate persistent asthma patients by decreasing nocturnal symptoms and the need for rescue medications.