Francesca Santamaria

Structural and Functional Lung Disease in Primary Ciliary Dyskinesia

BACKGROUND High-resolution CT (HRCT) scan data on primary ciliary dyskinesia (PCD) related lung disease are scarce. STUDY OBJECTIVES We evaluated the lung disease in children and adults with PCD by a modified Brody composite HRCT scan score to assess the prevalence of the structural abnormalities; to evaluate the correlation among HRCT scan scores, spirometry findings, and clinical data; and to compare the PCD scores with those of age-matched and sex-matched cystic fibrosis (CF) patients. PATIENTS AND METHODS Twenty PCD patients (age range, 4.6 to 27.5 years) underwent HRCT scanning, spirometry, and deep throat or sputum culture. A modified Brody score was used to assess bronchiectasis, mucous plugging, peribronchial thickening, parenchyma abnormalities, and mosaic perfusion. RESULTS The total HRCT scan score was 6% of the maximal score (range, 0.5 to 25.5). Subscores were as follows: bronchiectasis, 5.6%; mucous plugging, 5.6%; peribronchial thickening, 8.3%; parenchyma, 3%; and mosaic perfusion, 0%. The prevalence of lung changes were as follows: bronchiectasis, 80%; peribronchial thickening, 80%; mucous plugging, 75%; parenchyma, 65%; and mosaic perfusion, 45%. Sixteen of 19 PCD patients had positive culture findings, and the most common pathogen found was Haemophilus influenzae (84%). The total HRCT scan score was significantly related to age (p = 0.006), FEV(1) (p = 0.02), and FVC (p = 0.02). The bronchiectasis subscore was significantly related to FEV(1) (p = 0.04) and FVC (p = 0.03). In CF patients, the total HRCT scan score was significantly higher than that in PCD patients (p = 0.02). CONCLUSIONS PCD patients show significantly lower pulmonary HRCT scan scores than CF patients. The PCD total and bronchiectasis scores correlate with spirometry findings. The PCD HRCT scan score might be used for longitudinal assessment and/or represent an outcome surrogate in future studies.

Progression of lung disease in primary ciliary dyskinesia: Is spirometry less accurate than CT?

Despite its extensive use, there is no evidence that spirometry is useful in the assessment of progression of lung disease in primary ciliary dyskinesia (PCD). We hypothesize that high‐resolution computed tomography (HRCT) is a better indicator of PCD lung disease progression than spirometry. We retrospectively evaluated two paired spirometry and HRCT examinations from 20 PCD patients (age, 11.6 years; range, 6.5–27.5 years). The evaluations were performed in stable state and during unstable lung disease. HRCT scans were scored blind by two raters. Compared to the first assessment, at the second evaluation spirometry did not change while HRCT scores significantly worsened (P < 0.01). Age was significantly related to HRCT total (r = 0.5; P = 0.02) and bronchiectasis scores (r = 0.5; P = 0.02). At both evaluations, HRCT total score correlated with FEV1 (r = −0.5, P = 0.01; r = −0.7, P = 0.001, respectively) and FVC Z scores (r = −0.6, P = 0.006; r = −0.7, P = 0.001, respectively), and bronchiectasis score was related to FEV1 (r = −0.5, P = 0.03; r = −0.6; P = 0.002, respectively) and FVC Z scores (r = −0.6, P = 0.008; r = −0.7, P = 0.001, respectively). No relationship was found between the change in HRCT scores and the change in spirometry. In PCD, structural lung disease may worsen despite spirometry being stable. Pediatr Pulmonol. 2012; 47:498–504.

A Descriptive Study of Non-Cystic Fibrosis Bronchiectasis in a Pediatric Population from Central and Southern Italy

Background: Non-cystic fibrosis (CF) bronchiectasis is now identified more often than in the past. Objectives: It was the aim of this study to assess the high-resolution computed tomography (HRCT) localization and extent of bronchiectasis and to determine whether asthma status, atopy and bronchiectasis distribution are associated with the etiology of bronchiectasis. Methods: We retrospectively analyzed clinical, laboratory, functional and HRCT data of 105 children with non-CF bronchiectasis at 2 tertiary respiratory units in Italy. Forty cases had bronchiectasis associated with ongoing underlying conditions, namely primary ciliary dyskinesia, primary immunodeficiency or aspiration. Results: Age at the onset of chronic cough/wheeze and at the first X-ray-documented pneumonia as well as atopy prevalence were lower in patients with ongoing underlying conditions than in those without (p = 0.049, p = 0.003 and p = 0.0008, respectively). In most cases, bronchiectasis was multilobar, and a mean of 2.5 lobes were involved. The right side was more often involved than the left (88 vs. 70%; p = 0.002), and the upper lobes were relatively spared (p < 0.000001). Right lung involvement and multilobar disease were more prevalent in children younger than 2 years at first pneumonia (p < 0.05). Conclusions: Clinical information combined with laboratory data provides additional insights into the characteristics of non-CF bronchiectasis in a large population of Italian children. This study highlights the need for longitudinal evaluations, also using HRCT, of severe and non-resolving pneumonia in children.

Multicenter analysis of body mass index, lung function, and sputum microbiology in primary ciliary dyskinesia

No studies longitudinally, simultaneously assessed body mass index (BMI) and spirometry in primary ciliary dyskinesia (PCD).

Obesity Duration Is Associated to Pulmonary Function Impairment in Obese Subjects

Obesity is associated with pulmonary function disturbances. We hypothesized that lung function decreases with increasing duration of obesity. We evaluated pulmonary function tests (PFTs) in 188 nonsmoking subjects with primary obesity (aged 8–76 years; 36% with systemic hypertension). Duration of obesity was assessed by questionnaire in adults, and by height and weight growth patterns in children. Asthma and/or other allergic diseases were investigated by standardized questionnaires. BMI and BMI‐standard deviation scores (SDS) were 38.7 and 2.4 kg/m2, respectively. Forty‐six percent of patients were atopic. Among subjects with ever asthma (33%), 20 had current asthma (11% of the total). Forced vital capacity (FVC), forced expiratory volume in 1 s, total lung capacity (TLC), and functional residual capacity (FRC) were 103, 104, 95, and 76% predicted, respectively. Mean duration of obesity was 8.3 years. Compared with subjects who had been obese for ≤5 years, patients who had been obese for >15 years had significantly lower values on PFTs (P < 0.05). In subjects with systemic hypertension, PFTs were lower than in patients without hypertension (P < 0.01). Duration of obesity was significantly related to all PFTs (P ≤ 0.001). In a multiple regression analysis where duration and severity of obesity, hypertension, atopy, asthma, and family history of atopic diseases were independent variables, duration of obesity was a predictor of lower PFTs (P < 0.01). Of the remaining variables, only hypertension contributed to lower lung volumes. In obese individuals, lung function was significantly lower in subjects with greater years of obesity. Fat loss programs should be encouraged to prevent late pulmonary function impairment.

Clinical application of exhaled nitric oxide measurement in pediatric lung diseases

SummaryFractional exhaled nitric oxide (FeNO) is a non invasive method for assessing the inflammatory status of children with airway disease. Different ways to measure FeNO levels are currently available. The possibility of measuring FeNO levels in an office setting even in young children, and the commercial availability of portable devices, support the routine use of FeNO determination in the daily pediatric practice. Although many confounding factors may affect its measurement, FeNO is now widely used in the management of children with asthma, and seems to provide significantly higher diagnostic accuracy than lung function or bronchial challenge tests. The role of FeNO in airway infection (e.g. viral bronchiolitis and common acquired pneumonia), in bronchiectasis, or in cases with diffuse lung disease is less clear. This review focuses on the most recent advances and the current clinical applications of FeNO measurement in pediatric lung disease.

Measurement of nasal nitric oxide by hand‐held and stationary devices

Eur J Clin Invest 2011; 41 (10): 1063–1070

Obesity and pulmonary disease: unanswered questions

Obesity is associated with risk of pulmonary disease, and adversely affects lung function. The parallel increase in obesity and asthma suggests the two conditions are linked; indeed, they can worsen each other. Obesity and inadequate asthma control are associated with poor quality of life, and place a high economic burden on public health. Although the obesity–lung interaction is a major issue for basic research and clinical studies, various questions remain unanswered. Do intrauterine and early life factors impact on the development of obesity and lung disease? If so, can this be prevented? Asthma is generally more severe in obese subjects, but is adiposity a driver of a new asthma phenotype that features greater morbidity and mortality, worse control and decreased response to medications? Obese individuals have small lung volumes, hence their airway calibre is reduced and airway resistance is increased. What puzzles physicians is whether peripheral airways undergo remodelling, which would increase bronchoconstriction. Obese asthmatics respond suboptimally to anti‐inflammatory treatment, which raises the question: ‘what drug for what patient?’ Life expectancy is decreased in obesity and in chronic pulmonary disorders, but does obesity protect against or trigger chronic obstructive pulmonary disease? The time has come to find answers to these questions.

Sleep disordered breathing and airway disease in primary ciliary dyskinesia

Sleep‐disordered breathing (SDB) may develop in primary ciliary dyskinesia (PCD), leading to these diseases worsening one another.

Cardiopulmonary assessment in primary ciliary dyskinesia

Eur J Clin Invest 2012; 42 (6): 617–622