Opto-electronic Plethysmography Evaluation of Ventilatory and Thoraco-

abdominal Pattern in Children with Osteogenesis Imperfecta

Paolo Fraschini - IRCCS E.Medea - Bosisio Parini (LC) - Italy

Antonella Lo Mauro - Politecnico di Milano

Introduction• Osteogenesis Imperfecta (OI) is a congenital disease characterized by a disorder of

collagen metabolism and a consequent connective tissue disorder that affects different tissues with highly variable expression. For bone, this comprises fragility, osteopenia, reduced density, progressive deformity and disproportional growth (Kok 2013).

• The original classification of OI by Sillence based on clinical, radiographic and genetic characteristics identified one lethal (type II) and three nonlethal forms of the syndrome, namely type I, type IV and type III sorted by increasing severity according to the level of osteopenia, incidence of multiple fractures, severity of long bones bowing and degree of short stature. Life expectancy in these patients has been proven to be similar to the general population in type I, slightly reduced in type IV and impaired in type III before the age of 10 years (Paterson 1996).

• The main cause of death in OI patients is respiratory insufficiency resulting from impaired thoracic function worsened by ribcage deformity and scoliosis. Despite the incidence of the latter is higher in type III patients, it was found that scoliosis in this OI form is rare before the age of 6. After this age, the scoliotic deformity rapidly progresses until severe kyphoscoliosis is present in adulthood also in the mildest forms of the syndrome (Benson and Newman, 1981). Type III patients show pectus carinatum, a congenital deformity of anterior rib cage associated to severe vertebral platyspondilia, in which the abnormal growth of the sternum and costal cartilages result in an outward protrusion. As spinal deformity worsens the ribs assume a far more abnormal position further limiting the thoracic and therefore the lung expansion.

Introduction - 2• A correlation between reduced forced vital capacity and increasing thoracic scoliosis

was found (Widmann RF, 1999).

• Our group have also previously shown a significant relationship between the severity of ribcage deformity and the ventilator pattern at rest. Adult type III patients are characterized by pectus carinatum and show an altered respiratory muscles coordination, leading to paradoxical inspiratory inward motion of the pulmonary rib cage and significant rib cage distortions. On the other hand, the alterations in respiratory function were lower in the moderate type IV patients whose xiphosternal angle was normally flat (LoMauro 2012).

• None of the above cited papers, however, included children in their cohort of patients despite the hallmarks of the disease, i.e.: skeletal fragility and progressive deformity, are present since birth particularly in its severest form. The lack of this information can mainly be attributed to the fact that pulmonary function tests are not usually performed in children, being not easy to obtain reliable measures. It is crucial to include also respiratory evaluation in the clinical management of OI children because, as mentioned above, Paterson showed that in type III patients, 19 out of 26 deaths occurred before the age of 10. While the survival rate after this age had a better outlook.

• The aim of this paper was to study the ventilatory and the thoraco-abdominal pattern at rest, without requiring volitional maneuvers, in type III and type IV children before the age of 10. As sternal deformity is congenital, our hypothesis is that the severity-related profile found within the different subtypes of the disease in the breathing pattern of adults with OI has been present since childhood.

Materials and methods

• Fifteen children affected with osteogenesis imperfecta (OI) were recruited for this study. The most severe type III form of the disease was diagnosed in 7 children, the moderate type IV in 8 children. Nine healthy children were recruited as control group.

• Nine patients (5 type III and 4 type IV) were analyzed at least twice in the last 8 years according to their hospitalization. For these children, the most recent acquisition was considered in the overall group of patients.

Kinematic Analysis

• Total and compartmental chest wall volumes were measured by Opto-Electronic Plethysmography (OEP System; BTS, Milan, Italy).

• The system is based on eight infrared video cameras working at a sampling rate of 60 Hz. It provides the 3D coordinates of 52 retro-reflective markers placed, according to specific anatomical points, over the anterior chest wall surface from clavicles to pubis of the children lying supine on the bed (figure 1).

• Patients and healthy control were analyzed during three minutes of spontaneous quite breathing in awake diurnal state.

Chest wall dimensions and deformity

• In each subject, chest wall dimension and geometry were derived from markers’ 3D coordinates at the end of expiration.

• Total chest wall volume (VCW) enclosed by the markers was calculated by applied the Gauss’ theorem to surface triangulation, with markers being the vertexes of each triangle.

• Trunk height was assessed as the distance between the marker below the axilla and the marker on the ipsilateral iliac crest.

• To quantitatively describe the sternal deformity (‘pectus carinatum’) the angle subtended by the sternal lines on the transversal plane was calculated.

Chest wall volumes and ventilatory pattern.

• The volumes of the following three compartments, into which VCW can be split, were computed as well: pulmonary rib cage (VRC,P), under the action of inspiratory and expiratory rib cage muscle, abdominal rib cage (VRC,A), under the insertional action of the diaphragm and abdomen (VAB), submitted to the action of the diaphragm and the expiratory abdominal.

• From chest wall volume variation, the ventilatory pattern, in terms of minute ventilation, breathing frequency, tidal volume, rapid and shallow breathing and percentage contribution of each compartment to tidal volume was determined on a normalized breath obtained as mean of at least one minute of acquisition for OI and healthy children.

• Picture shows minute ventilation, its two components, namely breathing frequency and tidal volume, and rapid and shallow breathing (RBI) index, defined as the ratio of breathing frequency to tidal volume, in the three groups.

• There was no difference in minute ventilation between the three groups.

• Tidal volume of type III children was lower while breathing frequency significantly increase leading to higher RSB index.

• The ventilatory pattern of type IV differed from healthy children only for higher RSB index.

Chest wall compartment volumes and asynchrony

• Overall OI children were characterized by reduced thoracic contribution to tidal volume as shown in figure. The median percentage contribution of pulmonary rib cage to tidal volume was significantly lower, but positive, in OI type III patients compared to both type IV and healthy children (p<0.05). Difference in VRC,P contribution was also found in type IV children, being significantly lower than controls.

• Abdominal rib cage contribution to tidal volume was similar in the three groups like the contribution of the abdomen that had the tendency to be greater in type III but not significantly. No differences were found in the values of phase shift angle between volume variations of VRC,P and VAB (ΦTA) and within the two rib cage compartments (ΦRC) as shown in figure.

Longitudinal study

• The percentage contribution of pulmonary rib cage to tidal volume in the five OI type III children acquired longitudinally is shown in figure.

• It almost linearly declined with age approaching the inspiratory inward paradoxical area and the negative value previously found in adult type III patients.

• To be noticed that the child with negative values was the deceased one.

• The other parameters in type III patients and the ventilatory pattern of type IV children did not show such important longitudinal differences.

• We have shown that an altered breathing pattern in OI type III is present since childhood. This is characterized by rapid and shallow breathing associated with poor contribution of the pulmonary rib cage which further reduced with age becoming negative in adulthood.

• On the other hand, type IV children almost behaved like their healthy peers apart for an higher RSB index.

• We firmly believe that there is a strong correlation between the impaired thoracic expansion and the sternal deformity, as pectus carinatum is present only in type III children and it may alter the action of intercorstal muscles.

• This is an important set of data, since for the very first time it was taken into account how children affected by osteogenesis imperfecta breathed.

• This is important not only because the main cause of death in OI can be ascribed to respiratory complication, but mainly because the peak rate of mortality occurred within the first ten years of life, particularly in type III.

• Reliable spirometry is hard to obtain in children, because it requires cooperation from the patient.

• On the other hand, we considered the breathing pattern at rest, with the children put at ease on a comfortable bed without requiring any volitional maneuver. In addition, we provided information on the action of the different respiratory muscles.

• The diaphragm, the most important one, was preserved in OI children and sustained the ventilation.

• Ribcage muscles action, instead, was poor particularly in type III.

• These conclusions are in line with the results previously found in older OI patients with an important difference: children did not show either the inspiratory inward paradoxical movement of the pulmonary rib cage or the ribcage and chest wall distortion found in adulthood.

• They gradually approached to them as shown in the longitudinal study for the contribution of the pulmonary ribcage.

Conclusions• In OI type III children the combination of pectus

carinatum and brittle ribs put the intercostal muscles in mechanical disadvantage resulting in rapid and shallow breathing with a poor contribution of the pulmonary ribcage that worsen with age.

• Earlier achievement of inward inspiratory paradoxical movement of the pulmonary ribcage at rest in supine position could predict development of pulmonary complication.

• Type IV children showed higher rapid and shallow breathing, normal minute ventilation, regular respiratory muscles action and absence of sternal deformity