Background:
Although the 6-min walk test (6MWT) is the gold standard for assessing exercise-induced impairment of gas exchange, it cannot easily be performed in a clinical office environment. The aim ...of this study was to compare the 1-min sit-to-stand test (1STST) with the 6MWT for the ability to assess exercise-induced oxygen desaturation in patients with interstitial lung diseases (ILDs).
Methods:
A total of 107 patients were enrolled and classified into three groups: sarcoidosis, fibrotic idiopathic interstitial pneumonia (f-IIP), and other forms of ILD. The 6MWT and 1STST were performed on the same day, and pulmonary function tests, pulse oxygen saturation (SpO2), and dyspnea and fatigue (modified Borg scale) were assessed. SpO2 desaturation was evaluated by intraclass correlation coefficient (ICC), Bland–Altman analysis, and kappa (κ) coefficient in the whole population and the patient subgroups.
Results:
The SpO2 nadir during the 1STST and 6MWT showed good consistency mean ± standard deviation: 92.5% ± 5% and 90% ± 7%, respectively; ICC 0.77, 95% confidence interval (CI) 0.71–0.83 and correlated strongly (r = 0.9, p < 0.0001). The frequency of patients with oxygen desaturation ⩾4% was also consistent for the two exercise tests (κ = 0.68, 95% CI 0.54–0.82). The number of repetitions in the 1STST correlated with the 6MWT distance (r = 0.5, p < 0.0001), but the dyspnea scores were higher during the 1STST than the 6MWT (p < 0.0001). These findings did not differ for the three patient subgroups.
Conclusion:
The 1STST can measure exercise-induced desaturation in ILD patients and could be used as an alternative test to the 6MWT in office practice.
Lung infections play a critical role in cystic fibrosis (CF) pathogenesis. CF respiratory tract is now considered to be a polymicrobial niche and advances in high-throughput sequencing allowed to ...analyze its microbiota and mycobiota. However, no NGS studies until now have characterized both communities during CF pulmonary exacerbation (CFPE). Thirty-three sputa isolated from patients with and without CFPE were used for metagenomic high-throughput sequencing targeting 16S and ITS2 regions of bacterial and fungal rRNA. We built inter-kingdom network and adapted Phy-Lasso method to highlight correlations in compositional data. The decline in respiratory function was associated with a decrease in bacterial diversity. The inter-kingdom network revealed three main clusters organized around Aspergillus, Candida, and Scedosporium genera. Using Phy-Lasso method, we identified Aspergillus and Malassezia as relevantly associated with CFPE, and Scedosporium plus Pseudomonas with a decline in lung function. We corroborated in vitro the cross-domain interactions between Aspergillus and Streptococcus predicted by the correlation network. For the first time, we included documented mycobiome data into a version of the ecological Climax/Attack model that opens new lines of thoughts about the physiopathology of CF lung disease and future perspectives to improve its therapeutic management.
The aim of this study was to gain insight into the physiological changes occurring in subjects with cystic fibrosis (CF) after autogenic drainage (AD). Changes in respiratory system resistance (Rrs), ...reactance (Xrs), and spirometry were analyzed in adult CF subjects after a single AD physiotherapy session.
This prospective observational study was conducted during the annual check-up of adult CF subjects in stable condition. Spirometry and Rrs and Xrs measurements using the forced oscillations technique at 5, 11, and 19 hertz (Hz) were performed before and 30 min after a 20-min AD session. Control CF subjects were tested at baseline and 50 min without AD. Results are expressed as mean ± standard deviation or median interquartile range.
Thirty subjects were included in the physiotherapy group (age 29 25-34 years, forced expiratory volume in 1 s (FEV1) 40.3 30.1-57.9% predicted) and 11 in the control group (age 31 28.5-36.5 years, FEV1 43.6 31.1-51.9 % predicted). No significant changes in any parameter were observed in the control group. AD modestly but significantly increased the forced vital capacity (FVC) and FEV1 (p<0.001). Inspiratory resistance was also significantly improved by AD: Rrs5 from 5.74±2.39 to 5.24±2.17 cmH2O/L/s, p<0.05; Rrs11 from 4.83±1.98 to 4.32±1.7 cmH2O/L/s, p = 0.003; and Rrs19 from 4.18 3.46-5.07 to 3.86 2.76-4.98 cmH2O/L/s, p<0.001. In contrast, AD had no significant effects on frequency dependence of resistance (Rrs5-Rrs19) or expiratory resistance. Inspiratory Xrs5, but not ΔXrs5 (expiratory-inspiratory Xrs), was improved by AD (p<0.05). Moderate correlations were detected between the improvement in FEV1 and FVC and inspiratory resistance (r = 0.53, p = 0.005 and r = 0.44, p = 0.02, respectively).
A single session of AD improved inspiratory airway resistance, except in the distal airways. The forced oscillations technique provides a new tool for understanding the pathophysiological effects of airway clearance physiotherapy in CF.
A polymorphism on the MUC5B promoter (rs35705950) has been associated with idiopathic pulmonary fibrosis (IPF) but not with systemic sclerosis (SSc) with interstitial lung disease (ILD). We genotyped ...the MUC5B promoter in the first 142 patients of the French national prospective cohort of IPF, in 981 French patients with SSc (346 ILD), 598 Italian patients with SSc (207 ILD), 1383 French controls and 494 Italian controls. A meta-analysis was performed including all American data available. The T risk allele was present in 41.9% of the IPF patients, 10.8% of the controls (P = 2 × 10(-44)), OR 6.3 4.6-8.7 for heterozygous patients and OR 21.7 10.4-45.3 for homozygous patients. Prevalence of the T allele was not modified according to age, gender, smoking in IPF patients. However, none of the black patients with IPF presented the T allele. The prevalence of the T risk allele was similar between French (10%) and Italian (12%) cohorts of SSc whatever the presence of an ILD (11.1% and 13.5%, respectively). Meta-analysis confirmed the similarity between French, Italian and American cohorts of IPF or SSc-ILD. This study confirms 1) an association between the T allele risk and IPF, 2) an absence of association with SSc-ILD, suggesting different pathophysiology.
As miRNAs are associated with normal cellular processes, deregulation of miRNAs is thought to play a causative role in many complex diseases. Nevertheless, the precise contribution of miRNAs in ...fibrotic lung diseases, especially the idiopathic form (IPF), remains poorly understood. Given the poor response rate of IPF patients to current therapy, new insights into the pathogenic mechanisms controlling lung fibroblasts activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies for this devastating disease. To identify miRNAs with potential roles in lung fibrogenesis, we performed a genome-wide assessment of miRNA expression in lungs from two different mouse strains known for their distinct susceptibility to develop lung fibrosis after bleomycin exposure. This led to the identification of miR-199a-5p as the best miRNA candidate associated with bleomycin response. Importantly, miR-199a-5p pulmonary expression was also significantly increased in IPF patients (94 IPF versus 83 controls). In particular, levels of miR-199a-5p were selectively increased in myofibroblasts from injured mouse lungs and fibroblastic foci, a histologic feature associated with IPF. Therefore, miR-199a-5p profibrotic effects were further investigated in cultured lung fibroblasts: miR-199a-5p expression was induced upon TGFβ exposure, and ectopic expression of miR-199a-5p was sufficient to promote the pathogenic activation of pulmonary fibroblasts including proliferation, migration, invasion, and differentiation into myofibroblasts. In addition, we demonstrated that miR-199a-5p is a key effector of TGFβ signaling in lung fibroblasts by regulating CAV1, a critical mediator of pulmonary fibrosis. Remarkably, aberrant expression of miR-199a-5p was also found in unilateral ureteral obstruction mouse model of kidney fibrosis, as well as in both bile duct ligation and CCl4-induced mouse models of liver fibrosis, suggesting that dysregulation of miR-199a-5p represents a general mechanism contributing to the fibrotic process. MiR-199a-5p thus behaves as a major regulator of tissue fibrosis with therapeutic potency to treat fibroproliferative diseases.
The natural history of pulmonary Langerhans cell histiocytosis (PLCH) has been unclear due to the absence of prospective studies. The rate of patients who experience an early progression of their ...disease is unknown. Additionally, conflicting effects of smoking cessation on the outcome of PLCH have been reported.
In this prospective, multicentre study, 58 consecutive patients with newly diagnosed PLCH were comprehensively evaluated over a two-year period. Our objectives were to estimate the incidence of early progression of the disease and to evaluate the impact of smoking status on lung function outcomes. Lung function deterioration was defined as a decrease of at least 15% in FEV1 and/or FVC and/or DLCO, compared with baseline values. At each visit, smoking status was recorded based on the patients' self-reports and urinary cotinine measurements that were blinded for the patients. The cumulative incidence of lung function outcomes over time was estimated using the non-parametric Kaplan-Meier method. Multivariate Cox models with time-dependent covariates were used to calculate the hazards ratios of the lung function deterioration associated with smoking status with adjustment for potential confounders.
The cumulative incidence of lung function deterioration at 24 months was 38% (22% for FEV1 and DLCO, and 9% for FVC). In the multivariate analysis, smoking status and PaO2 at inclusion were the only factors associated with the risk of lung function deterioration. The patients' smoking statuses markedly changed over time. Only 20% of the patients quit using tobacco for the entire study period. Nevertheless, being a non-smoker was associated with a decreased risk of subsequent lung function deterioration, even after adjustment for baseline predictive factors. By serial lung computed tomography, the extent of cystic lesions increased in only 11% of patients.
Serial lung function evaluation on a three- to six-month basis is essential for the follow-up of patients with recently diagnosed PLCH to identify those who experience an early progression of their disease. These patients are highly addicted to tobacco, and robust efforts should be undertaken to include them in smoking cessation programs.
ClinicalTrials.gov: No: NCT01225601 .
Background The 6-min walk test (6MWT) is commonly used to assess exercise capacity in patients with fibrotic idiopathic interstitial pneumonia (f-IIP). However, it is not known whether patients with ...f-IIP have reduced levels of physical activity in daily life (DLPA) or whether pulmonary function tests and the 6MWT correlate with their DLPA. Methods The aim of this study was to measure DLPA in patients with f-IIP and to determine the relationships between DLPA and the 6MWT, pulmonary functional parameters, and anxiety and depression scores. Fifty patients with f-IIP and 25 sex- and age-matched healthy control subjects were enrolled. Markers of DLPA were assessed with a physical activity monitor for 4 consecutive days. Hospital Anxiety and Depression Scale (HADS) scores were evaluated. Results DLPA parameters were significantly reduced in patients with f-IIP compared with control subjects (all P < .001). The mean number of steps per day correlated strongly with diffusing capacity of the lung for carbon monoxide (D lco) , FVC, the 6MWT distance, and the 6MWT lowest oxygen saturation as measured by pulse oximetry (Sp o2 ). DLPA was unrelated to HADS scores. Multivariate analysis showed that D lco and 6MWT distance explained only 31% of the variance in the number of steps per day. D lco , 6MWT distance, 6MWT lowest Sp o2 , and DLPA were significant predictors of mortality, but only D lco and 6MWT distance were independent predictors. Conclusions Quantitation of DLPA is a novel patient-centered approach to assess function in f-IIP and may be a useful tool for clinical care and assessing response to therapy.
Few studies have examined the benefits of pulmonary rehabilitation in patients with fibrotic idiopathic pulmonary pneumonia (f-IIP). Here, we report the results of an observational study in routine ...clinical practice of home-based pulmonary rehabilitation for f-IIP patients.
A total of 112 consecutive patients (61 with idiopathic pulmonary fibrosis and 51 with fibrotic nonspecific interstitial pneumonitis) were enrolled, of whom 65 had mild-to-moderate disease (forced vital capacity (FVC) ≥50% predicted and diffusing capacity of the lung for carbon monoxide (
) ≥30% predicted) and 47 had severe disease (FVC <50% predicted and/or
<30% predicted). The 2-month pulmonary rehabilitation programme consisted of a once-weekly visit with retraining, therapeutic education and psychosocial support. Patients were provided with an individualised action plan and were followed-up bimonthly for 12 months. Exercise tolerance (6-min stepper test (6MST)), mood (Hospital Anxiety and Depression Scale (HADS)) and quality of life (QoL) (Visual Simplified Respiratory Questionnaire (VSRQ)) were assessed before (T
), immediately after (T
), 6 months after (T
) and 12 months after (T
) the end of the pulmonary rehabilitation programme.
6MST strokes, HADS Anxiety score and VSRQ score were each significantly improved at T
(n=101), T
(n=76) and T
(n=62) compared with T
values. The improvements in outcomes were not influenced by disease severity or subtype. Patients who completed the study had significantly better baseline FVC and
values than those who did not.
Home-based pulmonary rehabilitation provides long-term benefits in exercise tolerance, anxiety and QoL for patients with f-IIP. Pulmonary rehabilitation should be prescribed systematically as part of the therapeutic arsenal for these patients.
Pulmonary rehabilitation (PR) is a key treatment of chronic obstructive pulmonary disease (COPD) but studies are still needed to identify the most pertinent criteria to personalize this intervention ...and improve its efficacy.
This real-life retrospective study compared the effects of home-based PR on exercise tolerance, anxiety, depression, and health-related quality of life (HRQoL) in COPD patients, according to their medical equipment.
Exercise tolerance, anxiety, depression, and HRQoL were evaluated in 109 patients equipped with long-term oxygen therapy (LTOT), 84 patients with noninvasive ventilation (NIV), 25 patients with continuous positive airway pressure (CPAP), and 80 patients with no equipment (NE), before, just after, and 6 and 12 months after PR.
At baseline, the body mass index in the CPAP and NIV groups was higher (
<0.05) than in the other two groups, and the forced expiratory volume in 1 second was lower in the LTOT and NIV groups (
<0.001). All parameters improved after PR in the four groups (
<0.05), but for exercise tolerance, only the 6-minute stepper test showed maintained improvement after 6 and 12 months, whereas the 10 times sit-to-stand and timed up-and-go tests were only improved just after PR. At every time point, exercise tolerance was lower in the LTOT group (
<0.05), with a similar trend in the NIV group.
Despite differences in the medical equipment to treat COPD, home-based PR showed comparable feasibility, safety, and efficacy in all equipment-based groups. Medical equipment should therefore not be a barrier to home-based PR.
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