Human diaphragm atrophy in amyotrophic lateral sclerosis is not predicted by routine respiratory measures
Raquel Guimarães-Costa, Thomas Similowski, Isabelle Rivals, Capucine Morélot-Panzini, Marie-Cécile Nierat, Mai Thao Bui, David Akbar, Christian Straus, Norma Beatriz Romero, Patrick Pierre Michel, Fabrice Menegaux, François Salachas, Jésus Gonzalez-Bermejo, Gaëlle Bruneteau, RespiStimALS team, contributors to the RespiStimALS study were:, Maria Del Mar Amador, Jean Christophe Antoine, Marie Christine Arne-Bes, Valérie Attali, Katell Beauvais, Veronique Brunaud-Danel, Gaelle Bruneteau, Jean-Philippe Camdessanche, William Camu, Laurence Carluer, Julien Cassereau, Maud Chapart, Bruno Chenuel, Nathalie Chereau, Pascal Cintas, Pierre Clavelou, Philippe Corcia, André Cornette, Philippe Couratier, Isabelle Court-Fortune, Antoine Cuvelier, Christophe Delclaux, Claude Desnuelle, Sophie Di Maria, Catherine Fargeot, Brigitte Fauroux, Armelle Finet-Monnier, Marie Celine Fleury, Carmen Gaillat, Marjolaine Georges, Maurice Giroud, Jesus Gonzalez-Bermejo, Annick Greil, Muriel Guerrier, Guillaume Nicolas, Nathalie Guy, Didier Hannequin, Valérie Juillien, Raul Juntas-Morales, Romain Kessler, Yvan Kolev, Julien Lagarde, Geraldine Lautrette, Pierre Le Cam, Nadine LeForestier, Gwendal Lemasson, Thimothée Lenglet, Pascal Magro, Anne Mallart, Olivier Martinaud, Vincent Meininger, Fabrice Menegaux, Nicole Meslier, Pierre Moirot, Capucine Morelot-Panzini, Yann Nadjar, Myriam Niel-Duriez, Marie-Cecile Nierat, Severine Noullet, Nicolas Pageot, Thierry Perez, Christophe Perrin, Odile Pillet, Sophie Pittion, Jean Pouget, Pierre-François Pradat, Hélène Prigent, Claudio Rabec, Jean-Damien Ricard, Norma Romero, Catherine Royer, François Salachas, Barbara Schaup, Kamila Sedkaoui, Thomas Similowski, Marie-Hélène Soriani, Christian Straus, Marie-Laure Tanguy, Christine Tranchant, Nadia Vandenberghe, Annie Vershueren, Fausto Viader, Anne-Cecile Wienalek-Bachelet, Raquel Guimarães-Costa, Thomas Similowski, Isabelle Rivals, Capucine Morélot-Panzini, Marie-Cécile Nierat, Mai Thao Bui, David Akbar, Christian Straus, Norma Beatriz Romero, Patrick Pierre Michel, Fabrice Menegaux, François Salachas, Jésus Gonzalez-Bermejo, Gaëlle Bruneteau, RespiStimALS team, contributors to the RespiStimALS study were:, Maria Del Mar Amador, Jean Christophe Antoine, Marie Christine Arne-Bes, Valérie Attali, Katell Beauvais, Veronique Brunaud-Danel, Gaelle Bruneteau, Jean-Philippe Camdessanche, William Camu, Laurence Carluer, Julien Cassereau, Maud Chapart, Bruno Chenuel, Nathalie Chereau, Pascal Cintas, Pierre Clavelou, Philippe Corcia, André Cornette, Philippe Couratier, Isabelle Court-Fortune, Antoine Cuvelier, Christophe Delclaux, Claude Desnuelle, Sophie Di Maria, Catherine Fargeot, Brigitte Fauroux, Armelle Finet-Monnier, Marie Celine Fleury, Carmen Gaillat, Marjolaine Georges, Maurice Giroud, Jesus Gonzalez-Bermejo, Annick Greil, Muriel Guerrier, Guillaume Nicolas, Nathalie Guy, Didier Hannequin, Valérie Juillien, Raul Juntas-Morales, Romain Kessler, Yvan Kolev, Julien Lagarde, Geraldine Lautrette, Pierre Le Cam, Nadine LeForestier, Gwendal Lemasson, Thimothée Lenglet, Pascal Magro, Anne Mallart, Olivier Martinaud, Vincent Meininger, Fabrice Menegaux, Nicole Meslier, Pierre Moirot, Capucine Morelot-Panzini, Yann Nadjar, Myriam Niel-Duriez, Marie-Cecile Nierat, Severine Noullet, Nicolas Pageot, Thierry Perez, Christophe Perrin, Odile Pillet, Sophie Pittion, Jean Pouget, Pierre-François Pradat, Hélène Prigent, Claudio Rabec, Jean-Damien Ricard, Norma Romero, Catherine Royer, François Salachas, Barbara Schaup, Kamila Sedkaoui, Thomas Similowski, Marie-Hélène Soriani, Christian Straus, Marie-Laure Tanguy, Christine Tranchant, Nadia Vandenberghe, Annie Vershueren, Fausto Viader, Anne-Cecile Wienalek-Bachelet
Abstract
Amyotrophic lateral sclerosis (ALS) patients show progressive respiratory muscle weakness leading to death from respiratory failure. However, there are no data on diaphragm histological changes in ALS patients and how they correlate with routine respiratory measurements.We collected 39 diaphragm biopsies concomitantly with laparoscopic insertion of intradiaphragmatic electrodes during a randomised controlled trial evaluating early diaphragm pacing in ALS (https://ichgcp.net/clinical-trials-registry/NCT01583088" title="See in ClinicalTrials.gov">NCT01583088). Myofibre type, size and distribution were evaluated by immunofluorescence microscopy and correlated with spirometry, respiratory muscle strength and phrenic nerve conduction parameters. The relationship between these variables and diaphragm atrophy was assessed using multivariate regression models.All patients exhibited significant slow- and fast-twitch diaphragmatic atrophy. Vital capacity (VC), maximal inspiratory pressure, sniff nasal inspiratory pressure (SNIP) and twitch transdiaphragmatic pressure did not correlate with the severity of diaphragm atrophy. Inspiratory capacity (IC) correlated modestly with slow-twitch myofibre atrophy. Supine fall in VC correlated weakly with fast-twitch myofibre atrophy. Multivariate analysis showed that IC, SNIP and functional residual capacity were independent predictors of slow-twitch diaphragmatic atrophy, but not fast-twitch atrophy.Routine respiratory tests are poor predictors of diaphragm structural changes. Improved detection of diaphragm atrophy is essential for clinical practice and for management of trials specifically targeting diaphragm muscle function.
Conflict of interest statement
Conflict of interest: R. Guimarães-Costa has nothing to disclose. Conflict of interest: T. Similowski reports personal fees from AstraZeneca, Boerhinger Ingelheim France, GSK Lungpacer Inc., TEVA, Chiesi, Pierre Fabre and Invacare, and personal fees and non-financial support from Novartis, outside the submitted work. In addition, he received honoraria from Synapse Biomedical to translate the DPS/NeurRx4 user manual from English into French in 2007 and, from 2012 to 2016, Synapse Biomedical contributed to a fundraiser organised by T. Similowski to promote respiratory research. T. Similowski is also engaged in scientific collaborations with two other companies manufacturing phrenic stimulation devices. With Lungpacer Inc (Canada) he acts as a paid consultant and investigator in clinical trials, while with Atrotech-Neuroresp (France) he acts as a probono consultant (no fees or other support). Conflict of interest: I. Rivals has nothing to disclose. Conflict of interest: C. Morélot-Panzini has nothing to disclose. Conflict of interest: M-C. Nierat has nothing to disclose Conflict of interest: M.T. Bui has nothing to disclose. Conflict of interest: D. Akbar has nothing to disclose. Conflict of interest: C. Straus has nothing to disclose. Conflict of interest: N.B. Romero has nothing to disclose. Conflict of interest: P.P. Michel has nothing to disclose. Conflict of interest: F. Menegaux has nothing to disclose. Conflict of interest: F. Salachas has nothing to disclose. Conflict of interest: J. Gonzalez-Bermejo has nothing to disclose. Conflict of interest: G. Bruneteau has nothing to disclose.
Copyright ©ERS 2019.
Source: PubMed