The development of bronchiectasis on chest computed tomography in children with cystic fibrosis: can pre-stages be identified?

OBJECTIVE: Bronchiectasis is an important component of cystic fibrosis (CF) lung disease but little is known about its development. We aimed to study the development of bronchiectasis and identify determinants for rapid progression of bronchiectasis on chest CT. METHODS: Forty-three patients with CF with at least four consecutive biennial volumetric CTs were included. Areas with bronchiectasis on the most recent CT were marked as regions of interest (ROIs). These ROIs were generated on all preceding CTs using deformable image registration. Observers indicated whether: bronchiectasis, mucus plugging, airway wall thickening, atelectasis/consolidation or normal airways were present in the ROIs. RESULTS: We identified 362 ROIs on the most recent CT. In 187 (51.7 %) ROIs bronchiectasis was present on all preceding CTs, while 175 ROIs showed development of bronchiectasis. In 139/175 (79.4 %) no pre-stages of bronchiectasis were identified. In 36/175 (20.6 %) bronchiectatic airways the following pre-stages were identified: mucus plugging (17.7 %), airway wall thickening (1.7 %) or atelectasis/consolidation (1.1 %). Pancreatic insufficiency was more prevalent in the rapid progressors compared to the slow progressors (p = 0.05). CONCLUSION: Most bronchiectatic airways developed within 2 years without visible pre-stages, underlining the treacherous nature of CF lung disease. Mucus plugging was the most frequent pre-stage. KEY POINTS: • Development of bronchiectasis in cystic fibrosis lung disease on CT. • Most bronchiectatic airways developed within 2 years without pre-stages. • The most frequently identified pre-stage was mucus plugging. • This study underlines the treacherous nature of CF lung disease.

Validating chest MRI to detect and monitor cystic fibrosis lung disease in a pediatric cohort.

BACKGROUND: Computed Tomography (CT) is the gold standard to assess bronchiectasis and trapped air in cystic fibrosis (CF) lung disease, but has the disadvantage of radiation exposure. Magnetic Resonance Imaging (MRI) is a radiation free alternative. OBJECTIVE: To validate MRI as outcome measure by: correlating MRI scores for bronchiectasis and trapped air with clinical parameters, and by comparing those MRI scores with CT scores. METHODS: In patients with CF (aged 5.6-17.4 years), MRI and CT were alternated annually during routine annual check-ups between July 2007 and January 2010. Twenty-three children had an MRI performed 1 year prior to CT, 34 children had a CT 1 year prior to MRI. Bronchiectasis and trapped air were scored using the CF-MRI and CF-CT scoring system. CF-MRI scores were correlated with clinical parameters: FEV1 , Pseudomonas aeruginosa, pulmonary exacerbations and patient-reported respiratory symptoms measured on the Cystic Fibrosis Questionnaire-Revised (CFQ-R), using Spearman's correlation coefficient. MRI and CT scores were compared using intra-class correlation coefficients (ICC) and Bland-Altman plots. RESULTS: Fifty-seven patients who had an MRI, CT and CFQ-R during the study period were included. CF-MRI bronchiectasis correlated with FEV1 , Pseudomonas aeruginosa, pulmonary exacerbations and patient-reported respiratory symptoms. CF-MRI trapped air only correlated with FEV1 and Pseudomonas aeruginosa. ICCs between MRI and CT bronchiectasis and trapped air were 0.41 and 0.35 respectively. MRI tended to overestimate bronchiectasis compared to CT. CONCLUSION: The associations between CF-MRI scores and several important clinical parameters further contributes to the validation of MRI. MRI provides different information than CT.

Tracking CF disease progression with CT and respiratory symptoms in a cohort of children aged 6-19 years.

INTRODUCTION: Cystic fibrosis (CF) lung disease is characterized by bronchiectasis and trapped air on chest computed tomography (CT). OBJECTIVE: We aim to validate bronchiectasis and trapped air as outcome measures by evaluating associations between changes in bronchiectasis, trapped air and patient-reported respiratory symptoms. METHODS: A longitudinal cohort study has been conducted. CF patients (aged 6-19 years) who had two routine CTs and completed twice a Cystic Fibrosis Questionnaire-Revised within 2 years (referred to as T1 and T2 ), in the period of July 2007 to January 2012 were included. Bronchiectasis and trapped air were scored using the CF-CT scoring system. Correlation coefficients and student's paired t tests were performed. RESULTS: In total 40 patients were included with a median age at T1 of 12.6 years (range 6-17 years), and at T2 14.5 years (range 8-19 years). At T1 , bronchiectasis (r = -0.49, P < 0.01) and trapped air (r = -0.34, P = 0.04) correlated with CFQ-R Respiratory Symptoms Scores (CFQ-R RSS). At T2 similar correlations were found with the CFQ-R RSS. Over 2 years, there was significant progression in bronchiectasis (P = 0.03) and trapped air (P = 0.03), but not in CFQ-R RSS. Changes in bronchiectasis and trapped air were not associated with changes in CFQ-R RSS. CONCLUSION: Our results indicate that bronchiectasis and trapped are sensitive outcome measures in CF lung disease, showing a significant association with CFQ-R RSS at two-time points. However, progression of bronchiectasis and trapped air over 2 year does not necessarily correlate to changes in quality of life.

Impact of bronchiectasis and trapped air on quality of life and exacerbations in cystic fibrosis.

Cystic fibrosis (CF) is primarily characterised by bronchiectasis and trapped air on chest computed tomography (CT). The revised Cystic Fibrosis Questionnaire respiratory symptoms scale (CFQ-R RSS) measures health-related quality of life. To validate bronchiectasis, trapped air and CFQ-R RSS as outcome measures, we investigated correlations and predictive values for pulmonary exacerbations. CF patients (aged 6-20 years) underwent CT, CFQ-R RSS and 1-year follow-up. Bronchiectasis and trapped air were scored using the CF-CT scoring system. Correlation coefficients and backward multivariate modelling were used to identify predictors of pulmonary exacerbations. 40 children and 32 adolescents were included. CF-CT bronchiectasis (r = -0.38, p<0.001) and CF-CT trapped air (r = -0.35, p = 0.003) correlated with CFQ-R RSS. Pulmonary exacerbations were associated with: bronchiectasis (rate ratio 1.10, 95% CI 1.02-1.19; p = 0.009), trapped air (rate ratio 1.02, 95% CI 1.00-1.05; p = 0.034) and CFQ-R RSS (rate ratio 0.95, 95% CI 0.91-0.98; p = 0.002). The CFQ-R RSS was an independent predictor of pulmonary exacerbations (rate ratio 0.96, 95% CI 0.94-0.97; p<0.001). Bronchiectasis, trapped air and CFQ-R RSS were associated with pulmonary exacerbations. The CFQ-R RSS was an independent predictor. This study further validated bronchiectasis, trapped air and CFQ-R RSS as outcome measures in CF.

An evaluation of the thyrotrophin-releasing hormone stimulation test in paediatric clinical practice.

AIM: The aim of this retrospective study was to evaluate the clinical usefulness of the thyrotropin-releasing hormone (TRH) test in children with suspected hypothalamic or pituitary dysfunction. METHODS: We reviewed the case notes of all patients in whom a TRH test had been performed over a 6-year period. Group 1 (n = 85, 34 males, aged 0.9-18.8 years) was the reference group with no evidence of hypothalamic, pituitary or thyroid dysfunction. Group 2 (n = 42, 24 males, 0.1-18.0 years) were being investigated for possible pituitary or hypothalamic insufficiency. RESULTS: In Group 1, thyrotropin (TSH) responses were higher in females than males (p < 0.01). In Group 2, TSH responses were normal for gender in 26 patients, subnormal in 5, and exaggerated/delayed in 11. Four patients with normal TSH responses and 4 with exaggerated/delayed responses had persistently low free thyroxine (FT(4)) or later developed low FT(4) and were treated with thyroxine. All those with subnormal TSH responses had normal FT(4) and were not treated. The TRH test did not reliably discriminate between hypothalamic and pituitary disorders. CONCLUSIONS: The TRH test did not give useful clinical information. Clinical decisions regarding thyroxine treatment were based on FT(4), not the TRH test. The TRH test should be abandoned in paediatric practice.