Alain Palot

Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases.

Acetylcholine (neuronal and non-neuronal origin) regulates bronchoconstriction, and mucus secretion. It has an inflammatory effect by inducing attraction, survival and cytokine release from inflammatory cells. Muscarinic receptors throughout the bronchial tree are mainly restricted to muscarinic M1, M2 and M3 receptors. Three long-acting muscarinic receptor antagonists (LAMAs) were approved for the treatment of chronic obstructive pulmonary disease (COPD) in Europe: once-daily tiotropium bromide; once-daily glycopyrronium bromide; and twice-daily aclidinium bromide. All have higher selectivity for M3 receptors than for M2 receptors, and dissociate more slowly from the M3 receptors than they do from the M2 receptors. Some LAMAs showed anti-inflammatory effects [inhibition of neutrophil chemotactic activity and migration of alveolar neutrophils, decrease of several cytokines in the bronchoalveolar lavage (BAL) including interleukin (IL)-6, tumor necrosis factor (TNF)-α and leukotriene (LT)B4] and antiremodeling effects (inhibition of mucus gland hypertrophy and decrease in MUC5AC-positive goblet cell number, decrease in MUC5AC overexpression). In the clinic, LAMAs showed a significant improvement of forced expiratory volume in 1 second (FEV1), quality of life, dyspnea and reduced the number of exacerbations in COPD and more recently in asthma. This review will focus on the three LAMAs approved in Europe in the treatment of chronic airway diseases.

Home-based respiratory rehabilitation in adult patients with moderate or severe persistent asthma

Abstract Objective: We assessed retrospectively the feasibility of a home-based respiratory rehabilitation (RR) program for asthmatics under optimal pharmacological treatment, as this type of care can reduce costs and offer a more patient-friendly approach for subjects with persistent asthma. Methods: Fifty-two patients with persistent asthma were recruited to the RR program (20 males, 32 females, 54 ± 11 (SD) years, forced expiratory volume in one second 71 ± 33% of predicted mean value, BMI 29.9 ± 7.9 kg/m2). This two-month protocol comprised education sessions, respiratory physiotherapy and an exercise training program at home and in groups supervised by an adapted physical activity instructor. Results: Thirty-nine patients completed the whole RR program, i.e. 25% dropout. The dropout rate was significantly higher with respect to younger patients in employment. The number of exacerbations decreased significantly during the year following the program, regardless of whether the patients had dropped out (p < 0.02) or not (p < 0.001). The distance walked during a 6-min walking test increased by 33 m (p < 0.001). Several indices measured during a cycle ergometer test increased significantly after RR: peak oxygen uptake (10%), oxygen uptake at ventilatory threshold (12%) and maximum load (19%), all at a similar maximum heart rate. Concerning quality of life assessment, the Short-Form-36 Item Health Survey revealed a non-significant improvement in the “health change” item after RR (p < 0.07). Conclusions: This study demonstrates the potential of a home-based program in the treatment and rehabilitation of patients with asthma. Both functional and physiologic indices improved during the follow-up period.

We Should Prohibit Warfarin in Idiopathic Pulmonary Fibrosis

1. Villacorta M, Misari J. Perú: mapa del déficit habitacional a Nivel Distrital, 2007. INEI, Lima, Perú, 2007. 2. Diette GB, Accinelli RA, Balmes JR, Buist AS, Checkley W, Garbe P, Hansel NN, Kapil V, Gordon S, Lagat DK, et al. Obstructive lung disease and exposure to burning biomass fuel in the indoor environment. Glob Heart 2012;7:265–270. 3. Guofeng S, Siye W, Wen W, Yanyan Z, Yujia M, Bin W, Rong W, Wei L, Huizhong S, Ye H, et al. Emission factors, size distributions, and emission inventories of carbonaceous particulate matter from residential wood combustion in rural China. Environ Sci Technol 2012; 46:4207–4214. 4. Karottki DG, Bekö G, Clausen G, Madsen AM, Andersen ZJ, Massling A, Ketzel M, Ellermann T, Lund R, Sigsgaard T, et al. Cardiovascular and lung function in relation to outdoor and indoor exposure to fine and ultrafine particulate matter in middle-aged subjects. Environ Int 2014; 73:372–381. 5. Lam NL, Chen Y, Weyant C, Venkataraman C, Sadavarte P, Johnson MA, Smith KR, Brem BT, Arineitwe J, Ellis JE, et al. Household light makes global heat: high black carbon emissions from kerosene wick lamps. Environ Sci Technol 2012;46: 13531–13538. 6. Dogan OT, Elagoz S, Ozsahin SL, Epozturk K, Tuncer E, Akkurt I. Pulmonary toxicity of chronic exposure to tobacco and biomass smoke in rats. Clinics (Sao Paulo) 2011;66: 1081–1087. 7. Smith-Sivertsen T, Dı́az E, Pope D, Lie RT, Dı́az A, McCracken J, Bakke P, Arana B, Smith KR, Bruce N. Effect of reducing indoor air pollution on women’s respiratory symptoms and lung function: the RESPIRE Randomized Trial, Guatemala. Am J Epidemiol 2009; 170:211–220. 8. Bruce N, Neufeld L, Boy E, West C. Indoor biofuel air pollution and respiratory health: the role of confounding factors among women in highland Guatemala. Int J Epidemiol 1998;27: 454–458. 9. Jacobsen KH, Ribeiro PS, Quist BK, Rydbeck BV. Prevalence of intestinal parasites in young Quichua children in the highlands of rural Ecuador. J Health Popul Nutr 2007;25: 399–405. 10. Gamboa MI, Kozubsky LE, Costas ME, Garraza M, Cardozo MI, Susevich ML, Magistrello PN, Navone GT. Asociación entre geohelmintos y condiciones socioambientales en diferentes poblaciones humanas de Argentina [Associations between geohelminths and socioenvironmental conditions among different human populations in Argentina]. Rev Panam Salud Publica 2009;26:1–8.

La ventilation auto-asservie après SERVE-HF : le chant du cygne ?

Au terme d’un important travail d’analyse des études publiées sur la ventilation auto-asservie (VAA), Priou et al. ont communiqué dans la Revue des maladies respiratoires une synthèse visant à proposer des conduites pratiques et un éclairage sur les conséquences de l’étude SERVE-HF [1]. Avec le recul de l’impact de ces propositions sur la pratique quotidienne des cliniciens, certains points nous semblent devoir être précisés. Il existe un consensus en France entre sociétés savantes, tutelles et fabricants pour ne pas proposer une VAA chez les patients nouvellement diagnostiqués de phénotype « SERVEHF » (Tableau 1). Par contre, l’attitude vis-à-vis des patients de phénotype SERVE-HF déjà appareillés n’est pas consensuelle. L’Agence nationale de sécurité du médicament qui fait autorité sur l’utilisation des dispositifs médicaux en France a publié sur son site Internet les notes d’information de sécurité des trois fabricants de VAA. Ainsi, si le 13 mai 2015, le fabricant ResMed® promoteur de l’étude SERVEHF propose « l’arrêt immédiat de la VAA des patients déjà traités », le fabricant Philips Respironics® propose le 5 juin 2015 que « les patients actuellement appareillés doivent être évalués et l’éventualité de mettre fin à la thérapie par VAA doit être discutée », le fabricant Weinmann® proposant le même jour « il est toutefois déconseillé de mettre fin au traitement par VAA de façon incontrôlée et sans tenir compte de la situation individuelle ». Le caractère potentiellement médico-légal de ces informations de sécurité n’aura échappé à personne. Ces nuances et différences dans le positionnement des fabricants ne sont finalement que le reflet de celui de nos sociétés savantes. Si l’arrêt de la VAA est fortement recommandé par l’American Academy of Sleep Medi-