Systemic steroids are the standard treatment for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) despite their poor efficacy and disabling side ...effects.
To evaluate the effectiveness and tolerance of budesonide/formoterol as an alternative treatment for BOS after HSCT.
In this randomized, double-blind, placebo-controlled study, we randomly assigned 32 HSCT recipients with mild/severe BOS to receive budesonide/formoterol or placebo for 6 months. The primary outcome was the change in the FEV1 after 1 month of treatment (M1) compared with the baseline value. Patients were unblinded at M1 if there was no improvement in the FEV1. Those who had initially received placebo were switched to budesonide/formoterol. Intention-to-treat analysis was performed to assess the primary outcome. Additional analyses took scheduled treatment contamination into account.
At M1, the median FEV1 increased by 260 ml in the budesonide/formoterol arm compared with 5 ml in the placebo arm (P = 0.012). The median increases in the FEV1 at M1 relative to the baseline value for the treated and placebo groups were 13 and 0%, respectively (P = 0.019). Twenty-five patients received budesonide/formoterol during the study. The median difference in the FEV1 between the baseline and after 1 month of treatment for these patients was +240 ml (P = 0.0001). The effect of budesonide/formoterol on the FEV1 was maintained in the 13 patients who completed 6 months of treatment.
Budesonide/formoterol administration led to a significant improvement in the FEV1 in patients with mild/severe BOS after allogeneic HSCT. Clinical trial registered with www.clinicaltrials.gov (NCT00624754).
(1) Background: Systemic granulomatosis developed in a context of malignancy has already been reported. Our objective was to describe the clinical, radiological, functional, biological, and evolutive ...characteristics of sarcoidosis-like cancer-associated granulomatosis (SLCAG) and to compare them to those of sarcoidosis. (2) Methods: 38 patients with a biopsy-proven SLCAG developed after a diagnostic of malignancy were included. The control group consisted of sarcoidosis patients matched for age, sex, and radiologic stage. Clinical, biological, physiological, radiological, and outcome data were collected. (3) Results: The mean age of SLCAG patients was 51 ± 14 years. They were diagnosed within 15 ± 14 months of the cancer diagnosis (breast cancer most frequently). All SLCAG patients presented a thoracic involvement, extrathoracic locations were observed in 32% of subjects. SLCAG was more often asymptomatic than sarcoidosis (p < 0.0001). During follow-up, systemic treatment was less often required in SLCAG than in sarcoidosis (58% vs. 32%, p = 0.04 respectively) and SLCAG were characterized by a significantly less severe progression profile according to the Sarcoid Clinical Activity Classification, with a complete recovery more frequent at 5 years (p = 0.03). (4) Conclusion: This case-control study shows that SLCAG differs from sarcoidosis with a significantly more benign course. These results might argue for true differences in the physiopathology, which remain to be elucidated.
Background:
Idiopathic pulmonary fibrosis (IPF) is characterized by a male predominance. The aim of the study was to explore gender differences in a well-designed French multicentre prospective IPF ...cohort (COhorte FIbrose, COFI) with a 5-year follow-up.
Methods:
Between 2007 and 2010, 236 patients with incident IPF were included in COFI. Gender characteristics were compared using a
t
-test, Chi-squared test and ANOVA, as appropriate. Survival analyses were performed.
Results:
Fifty-one (22%) females and 185 (78%) males with an average age at diagnosis of 70.1 ± 9.20 and 67.4 ± 10.9 years, respectively, were included in the cohort. Women were significantly less exposed to tobacco smoke never
n
= 32 (62.7%) vs.
n
= 39 (21.1%),
p
< 0.001 and to occupational exposure
n
= 7 (13.7%) vs.
n
= 63 (34.1%),
p
= 0.012. Baseline forced vital capacity, % of predicted (FVC%) was significantly better in women compare to men (83.0% ± 25.0 v. 75.4% ± 18.7
p
= 0.046). At presentation honeycombing and emphysema on CT scan were less common in women
n
= 40 (78.4%) vs.
n
= 167 (90.3%)
p
= 0.041 and
n
= 6 (11.8%) vs.
n
= 48 (25.9%)
p
= 0.029, respectively. During follow-up fewer women were transplanted compared to men
n
= 1 (1.96%) vs.
n
= 20 (10.8%)
p
= 0.039. Medians of survival were comparable by gender 31 months (CI 95%: 28–40) vs. 40 months (CI 95%: 33–72)
p
= 0.2. After adjusting for age and FVC at inclusion, being a woman was not associated to a better survival.
Conclusions:
Women appear to have less advanced disease at diagnosis, maybe due to less exposure history compare to men. Disease progression and overall survival remains comparable regardless gender, but women have less access to lung transplantation.
Background: Dynamic hyperinflation (DH) develops in patients with COPD during incremental exercise with a cycle ergometer. The aims of
this study were to determine whether DH can be evidenced after ...walking with a handheld spirometer and to determine its functional
consequences.
Methods: Fifty patients with COPD (39 men; median age, 60 years interquartile range (IQR), 54 to 69 years; FEV 1 , 45% predicted IQR, 31 to 67% predicted) underwent pulmonary function tests and a 6-min walk test (6MWT). Inspiratory capacity
(IC) was measured with the patient in the standing position at rest and immediately after the 6MWT with a portable spirometer.
Dyspnea was evaluated directly (change in Borg score during 6MWT) and indirectly (Medical Research Council scale). The first
20 patients performed an incremental exercise test with cycle ergometer that allowed for the measurement of IC at peak exercise
and repeatedly during the first 3 min of recovery.
Results: The median change in IC during the 6MWT was â210 mL (IQR, 55 to â440; n = 50), whereas the median change in IC during the
exercise test was â295 mL (IQR, â145 to â515; n = 20). Both the IC and IC changes after 6MWT correlated to values after the
exercise test. DH decreased rapidly after the end of the exercise test but was nonsignificantly different from the baseline
value after 75 s of recovery. The percentage of decrease in IC during the 6MWT correlated with dyspnea (change in Borg score
during 6MWT: r 2 = 0.21; p = 0.0006).
Conclusions: DH can be measured during a 6MWT with a handheld spirometer to allow for its evaluation in daily practice and its contribution
to dyspnea while walking.
Benign metastasizing leiomyoma (BML) is a very rare condition and is characterized by the presence of benign smooth muscle tumours in organs distant from the uterus, most commonly the lung. It ...generally affects women of reproductive age and prognostic is usually excellent. However, the course of the disease is unpredictable. We report here the case of a 76‐year‐old woman with a previous medical history of uterine benign leiomyomas in whom BML was acutely revealed by a respiratory distress due to voluminous pulmonary and pleural leiomyomas requiring surgical extraction. Clinical evolution was remarkable by resistance to medical treatment and development of rare bone localization.
BML is a contradictory entity characterized by benign histological features but with metastatic potential. Pulmonologists as well as oncologists in charge of patients with multiple pulmonary nodules and a history of uterine leiomyoma should be aware of this potential diagnosis in order to implement appropriate diagnostic procedures for this benign tumour.
We report here the case of a 76‐year‐old woman with a previous medical history of uterine benign leiomyomas in whom benign metastasizing leiomyoma (BML), a very rare condition, was acutely revealed by a respiratory distress due to voluminous pulmonary and pleural leiomyomas requiring surgical extraction. Clinical evaluation was remarkable by resistance to medical treatment and development of rare bone localization.
Standard of care for interstitial lung disease (ILD) with a nonspecific interstitial pneumonia (NSIP) pattern proposes mycophenolate mofetil (MMF) as one of the first-step therapies while rituximab ...is used as rescue therapy.
In a randomised, double-blind, two-parallel group, placebo-controlled trial (NCT02990286), patients with connective tissue disease-associated ILD or idiopathic interstitial pneumonia (with or without autoimmune features) and a NSIP pattern (defined on NSIP pathological pattern or on integration of clinicobiological data and a NSIP-like high-resolution computed tomography pattern) were randomly assigned in a 1:1 ratio to receive rituximab (1000 mg) or placebo on day 1 and day 15 in addition to MMF (2 g daily) for 6 months. The primary end-point was the change in percent predicted forced vital capacity (FVC) from baseline to 6 months analysed by a linear mixed model for repeated measures analysis. Secondary end-points included progression-free survival (PFS) up to 6 months and safety.
Between January 2017 and January 2019, 122 randomised patients received at least one dose of rituximab (n=63) or placebo (n=59). The least-squares mean change from baseline to 6 months in FVC (% predicted) was +1.60 (se 1.13) in the rituximab+MMF group and -2.01 (se 1.17) in the placebo+MMF group (between-group difference 3.60, 95% CI 0.41-6.80; p=0.0273). PFS was better in the rituximab+MMF group (crude hazard ratio 0.47, 95% CI 0.23-0.96; p=0.03). Serious adverse events occurred in 26 (41%) patients of the rituximab+MMF group and in 23 (39%) of the placebo+MMF group. Nine infections were reported in the rituximab+MMF group (five bacterial infections, three viral infections, one other) and four bacterial infections in the placebo+MMF group.
Combination of rituximab and MMF was superior to MMF alone in patients with ILD and a NSIP pattern. The use of this combination must take into consideration the risk of viral infection.
The objectives of this prospective study were: 1) to determine the prevalence and determinants of obstructive sleep apnoea (OSA) in patients with newly diagnosed idiopathic pulmonary fibrosis (IPF); ...2) to determine whether OSA was associated with cardiovascular disease (CVD) as well as increased oxidative stress and levels of IPF biomarkers in the blood.A group of 45 patients with newly diagnosed IPF attended polysomnography. The prevalence of CVD and the severity of coronary artery calcification were investigated by high-resolution computed tomography. The levels of 8-hydroxydeoxyguanosine (8-OH-DG) and various IPF biomarkers in the blood were compared between patients with no or mild OSA (apnoea-hypopnoea index (AHI) <15 events·h
), with moderate OSA (15 ≤AHI <30 events·h
) and with severe OSA (AHI ≥30 events·h
).The prevalence of moderate-to-severe OSA and severe OSA was 62% and 40%, respectively. AHI did not correlate with demographic or physiological data. All patients with severe OSA had a medical history of CVD,
41.2% and 40% of those with no or mild OSA, or with moderate OSA, respectively (p<0.0001). Ischaemic heart disease (IHD) and moderate-to-severe coronary artery calcifications were strongly associated with severe OSA. The 8-OH-DG and matrix metalloproteinase-7 serum levels were significantly increased in the severe OSA group.Moderate-to-severe OSA is highly prevalent in incident IPF and severe OSA is strongly associated with the presence of CVD, particularly IHD.
Inorganic antigens may contribute to paediatric sarcoidosis. Thirty-six patients matched with 36 healthy controls as well as a group of 21 sickle-cell disease (SCD) controls answered an environmental ...questionnaire. Patients' indirect exposure to inorganic particles, through coresidents' occupations, was higher than in healthy and SCD controls (median score: 2.5 (0.5-7) vs 0.5 (0-2), p=0.003 and 1 (0-2), p=0.012, respectively), especially for construction, exposures to metal dust, talc, abrasive reagents and scouring products. Wood or fossil energies heating were also linked to paediatric sarcoidosis. This study supports a link between mineral environmental exposure due to adult coresident occupations and paediatric sarcoidosis.
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