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Pseudomonas aeruginosa (Pa) and Methicillin susceptible Staphylococcus aureus (MSSA) are the predominant bacteria found in the airways of people with cystic fibrosis (pwCF), significantly contributing to lung disease progression. While various factors influencing the initial acquisition (IA) of these pathogens are known, the impact of environmental conditions remains understudied. This epidemiological study assessed the risk of MSSA and Pa initial acquisitions in relation to seasonality and climatic zones among 1,184 French pwCF under 18 years old. The age at IA for Pa (Pa-IA) and MSSA (MSSA-IA) was estimated using the Kaplan–Meier method. Seasonality and climatic zones were analysed as risk factors using time-varying Cox regression models. The median age at MSSA-IA was notably earlier (2.0 years) than that at Pa-IA (5.1 years). MSSA-IA occurred increasingly younger in more recent birth cohorts, while the age at Pa-IA remained stable over time. The risk of Pa-IA was consistently higher in all seasons compared with spring, peaking in autumn (HR = 1.53), irrespective of climatic zones. In Oceanic and Continental climates, the highest risk for MSSA-IA was in winter (HRs = 1.45 and 1.20 respectively). In the Mediterranean climate, the risk of MSSA-IA was lower in winter compared to spring (HRs = 0.68 and 0.61 respectively), and the median age at MSSA-IA later than for Pa-IA. This study demonstrates that seasonality and meteorological factors may influence acquisition of MSSA and Pa in pwCF. These findings suggest that environmental factors play a role in pathogen acquisition dynamics in CF and could inform the development of preventive strategies. [ABSTRACT FROM AUTHOR]

Objective: Patients with systemic sclerosis and both pulmonary hypertension and interstitial lung disease (SSc–PH‐ILD) generally carry a worse prognosis than patients with SSc and pulmonary arterial hypertension (SSc‐PAH) without ILD. There is no evidence of the efficacy of PAH therapies in SSc–PH‐ILD. We undertook this study to compare survival of and response to treatment in patients with SSc–PH‐ILD and those with SSc‐PAH. Methods: We analyzed 128 patients (66 with SSc–PH‐ILD and 62 with SSc‐PAH) from 15 centers, in whom PH was diagnosed by right‐sided heart catheterization; they were prospectively included in the PH registry. All patients received PAH‐specific therapy. Computed tomography of the chest was used to confirm or exclude ILD. Results: At baseline, patients with SSc–PH‐ILD had less severe hemodynamic impairment than those with SSc‐PAH (pulmonary vascular resistance 5.7 Wood units versus 8.7 Wood units; P = 0.0005) and lower diffusing capacity for carbon monoxide (median 25% [interquartile range (IQR) 18%, 35%] versus 40% [IQR 31%, 51%]; P = 0.0005). Additionally, patients with SSc–PH‐ILD had increased mortality (8.1% at 1 year, 21.2% at 2 years, and 41.5% at 3 years) compared to those with SSc‐PAH (4.1%, 8.7%, and 21.4%, respectively; P = 0.04). Upon treatment with PAH‐targeted therapy, no improvement in the 6‐minute walk distance was observed in either group. Improvement in the World Health Organization functional class was observed less frequently in patients with SSc–ILD‐PH compared to those with SSc‐PAH (13.6% versus 33.3%; P = 0.02). Hemodynamics improved similarly in both groups. Conclusion: ILD confers a worse prognosis to SSc‐PH. Response to PAH‐specific therapy is clinically poor in SSc–PH‐ILD but was not found to be hemodynamically different from the response observed in SSc‐PAH. [ABSTRACT FROM AUTHOR]

Success of anti‐infective therapy is a major challenge in some patients given anatomo‐physiological changes and genetic variations. In this case anecdote, we report the management strategy of a patient suffering from chronic pulmonary aspergillosis in a context of anorexia nervosa and genetic polymorphism. [ABSTRACT FROM AUTHOR]

Background: Microbiological diagnosis of aspergillosis and triazole resistance is limited by poor culture yield. To better estimate this shortcoming, we compared culture and molecular detection of A. fumigatus in respiratory samples from French patients at risk for aspergillosis. Methods: A total of 97 respiratory samples including bronchoalveolar lavages (BAL), bronchial aspirates (BA), tracheal aspirates, sputa, pleural fluids, and lung biopsy were collected from 33 patients having invasive aspergillosis (n = 12), chronic pulmonary aspergillosis (n = 3), allergic bronchopulmonary aspergillosis (n = 7), or colonization (n = 11) and 28 controls. Each specimen was evaluated by culture, pan-Aspergillus qPCR, and CYP51A PCR and sequencing. Results: One A. flavus and 19 A. fumigatus with one multiazole resistant strain (5.3%) were cultured from 20 samples. Culture positivity was 62.5, 75, 42.9, and 15.8% in ABPA, CPA, IA, and colonized patients, respectively. Aspergillus detection rate was significantly higher by pan-Aspergillus qPCR than by culture in IA (90.5 vs. 42.9%; P < 0.05) and colonization group (73.7 vs. 15.8%; P < 0.05). The CYP51A PCR found one TR34/L98H along with 5 novel cyp51A mutations (4 non-synonymous and 1 promoter mutations), yet no association can be established currently between these novel mutations and azole resistance. The analysis of 11 matched pairs of BA and BAL samples found that 9/11 BA carried greater fungal load than BAL and CYP51A detection was more sensitive in BA than in BAL. Conclusion: Direct molecular detection of Aspergillus spp. and azole resistance markers are useful adjunct tools for comprehensive aspergillosis diagnosis. The observed superior diagnostic value of BAs to BAL fluids warrants more in-depth study. [ABSTRACT FROM AUTHOR]

Background: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission., Methods: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters., Results: Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo group (absolute difference -0.6%, 95% CI -16.8- +15.6%; OR 0.98, 95% CI 0.50-1.90; p=0.95). The median (interquartile range) time to first severe clinical exacerbation was longer in the liposomal amphotericin-B group: 337 days (168-476 days) versus 177 days (64-288 days). At the end of maintenance therapy, total immunoglobulin-E and Aspergillus precipitins were significantly decreased in the nebulised liposomal amphotericin-B group., Conclusions: In ABPA, maintenance therapy using nebulised liposomal amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research., Competing Interests: Conflict of interest: C. Godet reports having received speaker fees, travel support from Pfizer, MSD; fees for board memberships from SOS Oxygène and Pulmatrix; grant support from Ohre Pharma, Pfizer, MSD, SOS Oxygène, ISIS Medical and AstraZeneca. Conflict of interest: F. Couturaud reports having received research grant support from Bristol-Myers Squibb/Pfizer and fees for board memberships or symposia from Bayer, Bristol-Myers Squibb/Pfizer, Merck Sharp & Dohme and AstraZeneca, and having received travel support from Bayer, Bristol-Myers Squibb/Pfizer, Leo Pharma, Merck Sharp & Dohme and Actelion. Conflict of interest: S. Marchand-Adam reports having received consultancy for board membership, consultancy or speaker fees and travel support from AstraZeneca, Boehringer Ingelheim, Novartis and Roche. Conflict of interest: C. Pison reports having received, outside of the submitted work, consultancy for board membership, consultancy or speaker fees, travel support from AGIR à Dom, Chiesi, Boehringer Ingelheim, GSK, SOS Oxygène, AstraZeneca and Novartis. Conflict of interest: F. Gagnadoux reports having received grants and personal fees from Resmed; personal fees and non-financial support from Boehringer Ingelheim, Nyxoah, Sefam; personal fees from Actelion, Cidelec, Novartis, and non-financial support from Asten, unrelated to the submitted work. Conflict of interest: E. Blanchard reports having received consultancy or speaker fees, travel support from Pfizer, MSD, Novartis, Gilead, Roche, Boehringer Ingelheim, SOS Oxygene and ISIS Medical. Conflict of interest: C. Taillé reports having received consulting or advisory fees from Sanofi, GSK, AstraZeneca, Novartis and Chiesi, and research grants from Sanofi and GSK, outside the submitted work. Conflict of interest: B. Philippe reports having received speaker fees, travel support from Chiesi, Novartis and Oxyvie. Conflict of interest: S. Hirschi reports having received research grant support from CSL Behring and Adiral, and fees for board membership from Boehringer Ingelheim and Roche. Conflict of interest: C. Andréjak reports having received fees for board memberships or symposia and travel support from GSK, AstraZeneca, Zambon and Insmed. Conflict of interest: A. Bourdin reports having received grants from AstraZeneca, Boehringer Ingelheim, Cephalon/TEVA, GlaxoSmithKline, Novartis and Sanofi-Regeneron; has provided consultancy for Actelion, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, MedinCell, Merck, Novartis, Roche and Sanofi-Regeneron; and has acted as an investigator or co-investigator for trials sponsored by Actelion, AstraZeneca, Boehringer Ingelheim, Chiesi, Galapagos, GlaxoSmithKline, Merck, Novartis, Roche, Sanofi-Regeneron and Vertex. Conflict of interest: C. Chenivesse reports having received grants from AstraZeneca and Santelys outside the submitted work, personal fees from ALK-Abello, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKlein, Novartis, Sanofi-Regeneron and TEVA outside the submitted work and congress support from ALK-Abello, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pierre Fabre, Pfizer, Roche and TEVA. Conflict of interest: S. Dominique reports having received consultancy for board membership, speaker fees, travel support from Roche, Chiesi, Boehringer Ingelheim, AstraZeneca, Novartis and Actelion, outside the submitted work. Conflict of interest: L. Bassinet has nothing to disclose. Conflict of interest: M. Murris-Espin reports having received consultancy for board membership or speaker fees, or travel support, from Insmed, MSD, Pfizer, Asten, LVL, Vertex, Vivisol and Zambon. Conflict of interest: F. Rivière reports having received consultancy fees from Roche and Boehringer Ingelheim. Conflict of interest: G. Garcia reports having received grants from AstraZeneca, GlaxoSmithKline, Novartis, Sanofi-Regeneron and Chiesi; has provided consultancy for AstraZeneca, GlaxoSmithKline, Novartis and Sanofi-Regeneron; and has acted as an investigator or co-investigator for trials sponsored by AstraZeneca, GlaxoSmithKline and Sanofi-Regeneron. Conflict of interest: D. Caillaud reports having received consultancy or speaker fees, travel support from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini and Novartis. Conflict of interest: F-X. Blanc has nothing to disclose. Conflict of interest: F. Goupil reports having received travel support from Aliseo/Asten Santé, GSK, Chiesi, Novartis and Actelion. Conflict of interest: A. Bergeron reports having received consultancy or speaker fees, from Pfizer, Gilead, MSD, AstraZeneca and Takeda, and grants from SOS Oxygene. Conflict of interest: A. Gondouin reports having received consultancy or speaker fees, or travel support from Roche, Boehringer Ingelheim, Vitalaire, Actelion, LFB, GSK and Pfizer. Conflict of interest: J-P. Frat reports having received grants from the French Ministry of Health, outside the submitted work; grants, personal fees and non-financial support from Fisher & Paykel HealthCare, outside the submitted work; personal fees and non-financial support from SOS Oxygène, outside the submitted work. Conflict of interest: T. Flament has nothing to disclose. Conflict of interest: B. Camara reports having received outside of the submitted work, consultancy for speaker fees, travel supports from AGIR à Dom. Conflict of interest: P. Priou received travel support from Asten Santé. Conflict of interest: A-L. Brun has nothing to disclose. Conflict of interest: F. Laurent reports having received consultancy for board membership, consultancy or speaker fees, travel support from Bayer, Roche, Chiesi, Boehringer Ingelheim, SOS Oxygène, AstraZeneca, Basilea, Novartis and Actelion. Conflict of interest: S. Ragot has nothing to disclose. Conflict of interest: J. Cadranel reports having received speaker fees from MSD and Pfizer., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Enhanced lung angiogenesis has been reported in cystic fibrosis (CF). Recently, two highly homologous ligands, endocrine gland vascular endothelial growth factor (EG-VEGF) and mammalian Bv8, have been described as new angiogenic factors. Both ligands bind and activate two closely related G protein-coupled receptors, the prokineticin receptor (PROKR) 1 and 2. Yet, the expression, regulation, and potential role of EG-VEGF, BV8, and their receptors in normal and CF lung are still unknown. The expression of the receptors and their ligands was examined using molecular, biochemical, and immunocytochemistry analyses in lungs obtained from CF patients vs. control and in normal and CF bronchial epithelial cells. Cystic fibrosis transmembrane conductance regulator (CFTR) activity was evaluated in relation to both ligands, and concentrations of EG-VEGF were measured by ELISA. At the mRNA level, EG-VEGF, BV8, and PROKR2 gene expression was, respectively, approximately five, four, and two times higher in CF lungs compared with the controls. At the cellular level, both the ligands and their receptors showed elevated expressions in the CF condition. Similar results were observed at the protein level. The EG-VEGF secretion was apical and was approximately two times higher in CF compared with the normal epithelial cells. This secretion was increased following the inhibition of CFTR chloride channel activity. More importantly, EG-VEGF and BV8 increased the intracellular concentration of Ca(2+) and cAMP and stimulated CFTR-chloride channel activity. Altogether, these data suggest local roles for epithelial BV8 and EG-VEGF in the CF airway peribronchial vascular remodeling and highlighted the role of CFTR activity in both ligand biosynthesis and secretion., (Copyright © 2015 the American Physiological Society.)

Background: After lung transplantation (LT), immunoglobulin (Ig) G plasma concentrations<6 g/L are common and correlate with an increased risk of chronic lung allograft dysfunction (CLAD) and a poorer survival., Methods: We conducted an open substitution intervention with nonspecific intravenous Ig (IVIg), in all patients with IgG plasma less than 6 g/L post-LT in 54 of 84 consecutive recipients since 1998 who survived more than 3 months. Pre-LT and post-LT events were retrospectively analyzed., Results: Both substituted and nonsubstituted groups demonstrated similar donor or recipient characteristics and events over a median follow-up of 2.8 years (Q1-Q3, 1.4-5.7], except for initial diagnosis with more chronic obstructive pulmonary disease patients and less cases of pulmonary arterial hypertension in NS group. Intravenous Ig substitution started 3.5 months (0.5-9.4) after transplantation and lasted 4.5 months after (1.0-17.7), mean cumulative dose was 52.8±47.7 g. In multivariate Cox regression model, hypogammaglobulinemic patients who were substituted with IVIg had actually a 5-year survival (hazard ratio, 0.63; 95% confidence interval, 0.26-1.49; P=0.29) and CLAD-free 5-year survival (hazard ratio, 0.51; 95% confidence interval, 0.15-1.67; P=0.27) really close to nonhypogammaglobulinemic and nonsubstituted patients. Complementary analysis using propensity score and time-dependent analysis showed that survival and CLAD-free survival were not different in both groups., Conclusion: Intravenous Ig post-LT achieved similar survival and CLAD-free survival in recipients with hypogammaglobulinemia as compared to those with normal IgG plasmatic rate. A randomized control trial is required to confirm benefic effects of IVIg and disentangle mechanisms, including protection from infections, acute cellular and humoral rejections in patients with hypogammaglobulinemia after LT.