Search

Although scoliosis is defined as a Cobb angle of 10° or more as measured in the coronal plane, the combined three-dimensional distortions to both the spine and rib cage in scoliosis are best conceptualised as a thoracic deformity. There is much interest in the relationship between scoliosis and pulmonary function due to the increased morbidity of respiratory failure and mortality of those with untreated progressive scoliosis. Establishing the mechanisms of pulmonary function impairment in scoliosis is important in identifying patients with compromised lung function or those who will benefit from surgical intervention. In this work, the relationship between thoracic deformity in patients with right-sided, Lenke type 1 or 2, adolescent idiopathic scoliosis (AIS) and pulmonary function impairment is investigated. From radiographic and computer tomographic imaging, measurements of the thoracic deformity were found to be superior predictors of pulmonary function in AIS than conventional Cobb angles. A statistical shape model was constructed from biplanar radiographs to identify modes of variation in the thoracic configuration. Thoracic features such as the extent of the rib hump, narrowed convex hemithoracic width and spinal intrusion were found to be factors contributing to lung function impairment. Morphological analysis of the tracheobronchial tree demonstrated the presence of right-sided airway narrowing. In particular, patients with hypokyphosis demonstrated significant narrowing of the bronchus intermedius and its bifurcation as a result of extrinsic compression by the vertebral column. Right-sided airway obstruction was found to correspond to the presence of atelectasis and air-trapping in the right middle and lower lobe. Post-operative analysis demonstrated that restoration of natural kyphosis in patients with hypokyphosis and scoliosis resulted in improved lung function post-operatively. Although reduction in lung function in patients with scoliosis is multifactorial, variance in the sagittal thoracic profile plays a more important role in impairing lung function than is generally appreciated.

The mucopolysaccharidoses are a family of seven rare inherited metabolic disorders caused by specific lysosomal enzyme deficiencies responsible for catabolism of glycosaminoglycan (GAG) substrates. Subsequent accumulation of partially degraded GAGs leads to cellular dysfunction and progressive multisystem disease, presenting with visceral, cardiorespiratory, musculoskeletal and neurocognitive manifestations. The severe form of MPS I, Hurler syndrome, may be successfully treated with haematopoietic stem cell transplant (HSCT), while attenuated forms of MPS I and MPS II, IVA and VI are currently managed with enzyme replacement therapy. Progressive, multilevel airway and respiratory involvement is a well-recognised feature of a number of types of MPS and contributes to the premature morbidity and mortality seen in this disease. The literature regarding this aspect of disease is limited and current knowledge is informed by descriptive studies of small cohorts. The association between outcomes, metabolic and aetiological factors have not been adequately investigated. Following formal systematic review methodology, we have quantitatively assessed the current literature on obstructive sleep apnoea (OSA) in MPS. The prevalence of OSA in MPS prior to treatment is 81%, with MPS I most severely affected. Subsequent assessment of a cohort of 61 MPS I patients, has demonstrated excellent long-term outcomes following HSCT, while identifying causal associations between clinical disease regression, measured by urinary substrate biomarkers, and an improvement in airway obstruction. Multivariate analysis has confirmed that early initiation of treatment and optimal donor selection in HSCT contributes to improved outcomes. Using assays to detect and quantify the function of inhibitory antibodies against ERT, we have identified a cohort of patients with impaired metabolic correction and severe airway obstruction. Finally, analysis of adenotonsillar samples donated by patients and examination of the respiratory tract in a murine model of MPS I allowed us to investigate aetiological factors contributing to airway pathology. Adenotonsillar tissue displayed evidence of alteration in extracellular matrix protein deposition, suggesting remodelling of tissue contributes to the obstructive phenotype observed in patients. We further demonstrated an absence of inflammation in both patient tissue samples and within the lower respiratory tract in mice. Overall, we have ascertained factors which may improve clinical outcomes in the management of airway disease and identified aetiological components contributing to the cascade of events leading to obstructive airway pathology in MPS.

Introduction: The Global Lung Function Initiative (GLI) has proposed new criteria for airflow limitation (AL) and recommends using these to interpret spirometry. The objective of this study was to explore the impact of the application of the AL GLI criteria in two well characterized GOLD-defined COPD cohorts. Methods: COPD patients from the BODE (n=360) and the COPD History Assessment In SpaiN (CHAIN) cohorts (n=722) were enrolled and followed. Age, gender, pack-years history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, history of exacerbations and survival were recorded. CT-detected comorbidities were registered in the BODE cohort. The proportion of subjects without AL by GLI criteria was determined in each cohort. The clinical, CT-detected comorbidity, and overall survival of these patients were evaluated. Results: In total, 18% of the BODE and 15% of the CHAIN cohort did not meet GLI AL criteria. In the BODE and CHAIN cohorts respectively, these patients had a high clinical burden (BODE≥3: 9% and 20%; mMRC≥2: 16% and 45%; exacerbations in the previous year: 31% and 9%; 6MWD

Abstract: Background: Exercise-induced bronchoconstriction (EIB), airway hyperresponsiveness (AHR), airway inflammation, and respiratory symptoms are commonly observed in competitive swimmers. High ventilation during pool training with cumulative exposure to chlorine by-products likely influences such respiratory problems, however there is paucity of evidence to explain whether varying amounts of training influence the lung health of competitive swimmers. Therefore, the objective of the study was to determine the effect of increasing external training loads and internal training stress (the individual response to training) on AHR, inflammation, and respiratory symptoms of competitive youth swimmers. Hypothesis: We hypothesized overall lung health status would worsen with increased training loads. We predicted lung health would be the worst following a high training load block compared to moderate or low training blocks. Methods: Eight competitive youth swimmers (4 males, 4 females) from the same high-performance swimming group completed three blocks of training (three weeks in duration) classified as Low, Moderate, and High based on calculations of prescribed swimming distance and intensity. Swimmers completed a weekly self-report questionnaire to determine respiratory symptoms. Session Rating of Perceived Exertion (RPE) was reported daily to quantify internal training stress, which reflects the internal training load (product of RPE and training duration), internal training monotony (daily mean of training loads divided by the standard deviation), and internal training strain (product of load and monotony). Eucapnic Voluntary Hyperpnea (EVH) challenge, spirometry pre- and post-EVH, and Fractional Exhaled Nitric Oxide (FeNO) were completed to determine the extent of AHR, EIB, and inflammation. Data from the three training were analyzed to determine whether an increase in training load resulted in significant differences in lung health measures across training blocks. Results: Swimmers had significantly decreased resting FEV1 after the Moderate training compared to Low, but there was no significant change after High. Maximum % decreases in FEV1 did not differ significantly across training blocks. Post-EVH FeNO after the Moderate block was also significantly decreased compared to Low. Internal load was significantly decreased after the Moderate block compared to High, while internal monotony was significantly decreased after Moderate compared to Low. Recovery from the EVH test (FEV1 at sampling intervals) was correlated with respiratory symptom frequency after training blocks. Conclusion: Increases in training load and monotony influence airway obstruction and inflammation in competitive youth swimmers. Swimmers in our study also had hyperresponsive airways, as revealed by the consistent decreases in FEV1 >10% upon provocation by EVH. Our results add to existing evidence that training with little variability in the daily training load (i.e. high monotony) may be a factor that facilitates the development of respiratory symptoms and could contribute to AHR and EIB in competitive swimmers. Thus, prescribing conservative increases in training load and maintaining low monotony in competitive swim programs may help reduce respiratory symptom frequency associated with EIB. However, further research is needed to determine the impact of varying training loads on long-term lung health and performance outcomes of swimmers over a season. Competitive swimming programs might benefit from implementing a lung health monitoring system that includes quantifying training loads, tracking respiratory symptoms, and measuring resting lung function.