Rib Cage Deformities Alter Respiratory Muscle Action and Chest Wall Function in Patients with Severe Osteogenesis Imperfecta Antonella LoMauro 1 , Simona Pochintesta 2 , Marianna Romei 2 , Maria Grazia D’Angelo 2 , Antonio Pedotti 1 , Anna Carla Turconi 2 , Andrea Aliverti 1 * 1 TBMLab, Dipartimento di Bioingegneria, Politecnico di Milano, Milano, Italy, 2 IRCCS E.Medea, Bosisio Parini (Lc), Italy Abstract Background: Osteogenesis imperfecta (OI) is an inherited connective tissue disorder characterized by bone fragility, multiple fractures and significant chest wall deformities. Cardiopulmonary insufficiency is the leading cause of death in these patients. Methods: Seven patients with severe OI type III, 15 with moderate OI type IV and 26 healthy subjects were studied. In addition to standard spirometry, rib cage geometry, breathing pattern and regional chest wall volume changes at rest in seated and supine position were assessed by opto-electronic plethysmography to investigate if structural modifications of the rib cage in OI have consequences on ventilatory pattern. One-way or two-way analysis of variance was performed to compare the results between the three groups and the two postures. Results: Both OI type III and IV patients showed reduced FVC and FEV 1 compared to predicted values, on condition that updated reference equations are considered. In both positions, ventilation was lower in OI patients than control because of lower tidal volume (p,0.01). In contrast to OI type IV patients, whose chest wall geometry and function was normal, OI type III patients were characterized by reduced (p,0.01) angle at the sternum (pectus carinatum), paradoxical inspiratory inward motion of the pulmonary rib cage, significant thoraco-abdominal asynchronies and rib cage distortions in supine position (p,0.001). Conclusions: In conclusion, the restrictive respiratory pattern of Osteogenesis Imperfecta is closely related to the severity of the disease and to the sternal deformities. Pectus carinatum characterizes OI type III patients and alters respiratory muscles coordination, leading to chest wall and rib cage distortions and an inefficient ventilator pattern. OI type IV is characterized by lower alterations in the respiratory function. These findings suggest that functional assessment and treatment of OI should be differentiated in these two forms of the disease. Citation: LoMauro A, Pochintesta S, Romei M, D’Angelo MG, Pedotti A, et al. (2012) Rib Cage Deformities Alter Respiratory Muscle Action and Chest Wall Function in Patients with Severe Osteogenesis Imperfecta. PLoS ONE 7(4): e35965. doi:10.1371/journal.pone.0035965 Editor: James West, Vanderbilt University Medical Center, United States of America Received November 15, 2011; Accepted March 27, 2012; Published April 27, 2012 Copyright: ß 2012 LoMauro et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by a grant of Fondazione Cariplo: Health Innovation Network Technology @ Lecco (HINT@Lecco). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: andrea.aliverti@polimi.it Introduction Osteogenesis imperfecta (OI) is a genetically heterogeneous group of congenital disorders of collagen synthesis characterized by brittle bones leading to different levels of skeletal deformities and frequent multiple fractures. OI exhibits a broad range of clinical severity, ranging from multiple fracturing in utero to normal adult stature and a low fracture incidence [1,2]. Although new types of OI syndrome have been recently introduced [3], the traditional classification proposed by Sillence et al. [4,5] considers four main groups according to the phenotypic variability, i.e. type I, II, III, and IV. OI type I is the mildest form characterized by blue sclerae; perinatal lethal OI type II, also known as congenital OI; OI type III, the most severe non-lethal form characterized by multiple fractures with normal sclera, progressive long bones, spine deformities and short stature; and OI type IV, a moderate form with normal sclerae [5–7]. Life expectancy in OI type IV is similar to general population, while in type III is reduced [8] with cardiopulmonary insufficiency and respiratory infections being the leading causes of death in these patients, and their prevention and treatment are important factors for prognosis [9,10]. Although it is reasonable to postulate that structural alterations of the chest wall, namely spinal and rib cage deformities, may contribute to cardiopulmonary problems in severe OI, few authors reported data on deformities and pulmonary function [11,12]. The hypothesis of the present paper is that structural modifications of the rib cage due to OI have important consequences on ventilation at rest in terms of chest wall function. To test this hypothesis we noninvasively measure kinematics and PLoS ONE | www.plosone.org 1 April 2012 | Volume 7 | Issue 4 | e35965