Sleep disordered breathing and airway disease in primary ciliary dyskinesia.

BACKGROUND AND OBJECTIVE: Sleep-disordered breathing (SDB) may develop in primary ciliary dyskinesia (PCD), leading to these diseases worsening one another. METHODS: Sixteen stable PCD patients (4.9-17.2 years) and 42 controls underwent overnight respiratory polysomnography (rPSG) and Sleep Disturbances Scale for Children (SDSC). In PCD we assessed nasal endoscopy, pulmonary function tests and chest high-resolution computed tomography (HRCT). RESULTS: Compared with controls, PCD had higher obstructive apnoea (4.7 vs 0.2, P < 0.001), central apnoea (0.8 vs 0.2, P < 0.001), hypopnoea (1.8 vs 0.2, P < 0.001), apnoea-hypopnoea (7.8 vs 0.6, P < 0.001), oxygen desaturation indexes (ODI; 0.7 vs 0.2, P = 0.002), and mean oxygen desaturation (4% vs 1%, P < 0.001), while mean and nadir oxygen saturation (97.1% vs 98.1, P < 0.001) (93% vs 97.2%, P < 0.001) were lower, respectively. In PCD, SDSC was unrelated to rPSG (P > 0.05), with total score and subscores of disorders in initiating and maintaining sleep, and sleep-wake transition lower than controls. PCD patients had chronic rhinosinusitis (100%) and adenoidal hypertrophy (50%). Total HRCT score was 7 (range 0-14). ODI correlated with functional residual capacity (r = 0.8, P = 0.02), total HRCT (r = 0.6, P = 0.03) and peribronchial thickening scores (r = 0.7, P = 0.02). Oxygen saturation was associated with bronchiectasis severity score (r = -0.6, P = 0.02). CONCLUSIONS: PCD's parents may underestimate SDB. As nocturnal desaturation is associated with lung function and structure abnormalities, SDB may significantly contribute to pulmonary morbidity.

Measurement of nasal nitric oxide by hand-held and stationary devices.

BACKGROUND: Nasal nitric oxide (nNO) is assessed by nasal aspiration/insufflation via one nostril or by nasal silent exhalation through a facemask and is also measured during humming, a manoeuvre that results in increased nNO in the presence of a patent osteomeatal complex. Humming nNO peak is absent in primary ciliary dyskinesia (PCD) and in cystic fibrosis (CF). Hand-held devices are used successfully for exhaled or nNO analysis. No study compared nNO during silent and humming exhalation using hand-held and stationary analysers. METHODS: Thirty-eight subjects (14 PCD; 11 CF; 13 healthy individuals) measured nNO with a stationary and a hand-held analyser during silent and humming exhalations. RESULTS: No difference between nNO obtained from stationary or hand-held analyser during silent and humming exhalation was found (P > 0·05). Patients with PCD exhibited lower silent and humming nNO than CF or controls (P < 0·001). During both silent and humming exhalation, there was a significant correlation between nNO from the two analyzers both in the whole study population and within each group (r ≥ 0·7, P < 0·01). Bland-Altman plots confirmed this agreement. Using the hand-held device during humming, nNO values of 50, 81 and 21 ppb had sensitivity and specificity > 90% for discriminating PCD or CF from healthy subjects, and patients with PCD from patients with CF, respectively. CONCLUSIONS: The hand-held device is as effective as the stationary analyzer for assessing nNO during silent and humming exhalation. Its wider use might result in an increased number of subjects suspected to have PCD.

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.

Respiratory manifestations in patients with inherited metabolic diseases.

Growing evidence indicates that inherited metabolic diseases are increasingly being recognised. Life expectancy for many patients is progressively improving because new therapeutic strategies are available. Because most inherited metabolic diseases are systemic disorders, virtually all organs may be involved. Respiratory disease complicates the management of several inherited metabolic diseases, either at presentation or as late-onset features. This review will describe the most exemplary respiratory manifestations of inherited metabolic diseases in childhood and adulthood. Since airways disease worsens the morbidity of many inherited metabolic disorders, leading to increased hospitalisations, mortality and overall healthcare costs, respiratory manifestations of inherited metabolic diseases need to be carefully recognised and treated. All patients with inherited metabolic disease and suspected airway disease should undergo a detailed diagnostic work-up. Current treatments for several inherited metabolic diseases (including enzyme replacement therapy, substrate reduction, bone marrow transplantation, or even more innovative strategies such as pharmacological chaperone or gene therapies) may provide significant benefits for associated respiratory disease. The integration of several specialists dedicated to airway disease management in a multidisciplinary team is essential to provide the most appropriate care to children and adults with inherited metabolic disease.

Psychological, cognitive and maternal stress assessment in children with primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare disorder due to structure and functional abnormalities of respiratory cilia. There are no reports on the behavioral and psychological aspects of children and adolescents with PCD. This study was undertaken to assess the cognitive and behavioural characteristics, and the parental stress of a population of school-aged children with PCD. METHODS: Ten PCD and 34 healthy school-aged children underwent Wechsler Intelligence Scale for Children-III edition, Child Behavior Check-List questionnaire (CBCL), Parenting Stress Index-Short Form tests in order to perform a behavioural and psychological evaluation. RESULTS: PCD children showed significant behavioral and social competent problems in CBCL scale than control children, in particular with regard to internalizing problems score (P<0.001). Parental distress, parent-child interaction and total stress in the mothers of PCD patients were higher than those in the controls' parents (P<0.001). CONCLUSION: Our findings pinpoint the importance of specific psychological support in the clinical management of children with PCD.

Hypertransaminasemia and fatal lung disease: a case report.

Glycogenosis type II (Pompe disease) is a rare autosomal recessive genetic disorder caused by mutations in the gene encoding the lysosomal enzyme acid α-glucosidase. The classic form is characterized by severe cardiac involvement, generalized hypotonia and exitus early in life. Presenting symptoms and signs of the disease may be neglected or underestimated, thus delaying the diagnosis. Respiratory manifestations mainly occur because of respiratory muscle weakness. However, additional mechanisms can favor the development of pulmonary complications that result in fatal respiratory failure. We herein describe a case of an infant with glycogenosis type II presenting with hepatomegaly and hypertransaminasemia, who rapidly developed fatal lung disease.

Update on leukotriene receptor antagonists in preschool children wheezing disorders.

Asthma is the most common chronic disease in young children. About 40% of all preschool children regularly wheeze during common cold infections. The heterogeneity of wheezing phenotypes early in life and various anatomical and emotional factors unique to young children present significant challenges in the clinical management of this problem. Anti-inflammatory therapy, mainly consisting of inhaled corticosteroids (ICS), is the cornerstone of asthma management. Since Leukotrienes (LTs) are chemical mediators of airway inflammation in asthma, the leukotriene receptor antagonists (LTRAs) are traditionally used as potent anti-inflammatory drugs in the long-term treatment of asthma in adults, adolescents, and school-age children. In particular, montelukast decreases airway inflammation, and has also a bronchoprotective effect. The main guidelines on asthma management have confirmed the clinical utility of LTRAs in children older than five years. In the present review we describe the most recent advances on the use of LTRAs in the treatment of preschool wheezing disorders. LTRAs are effective in young children with virus-induced wheeze and with multiple-trigger disease. Conflicting data do not allow to reach definitive conclusions on LTRAs efficacy in bronchiolitis or post-bronchiolitis wheeze, and in acute asthma. The excellent safety profile of montelukast and the possibility of oral administration, that entails better compliance from young children, represent the main strengths of its use in preschool children. Montelukast is a valid alternative to ICS especially in poorly compliant preschool children, or in subjects who show adverse effects related to long-term steroid therapy.

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/m(2), 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.

Nasal nitric oxide assessment in primary ciliary dyskinesia using aspiration, exhalation, and humming.

BACKGROUND: Several studies reported low nasal nitric oxide (nNO) levels in subjects with primary ciliary dyskinesia (PCD) and proposed nNO measurement as a diagnostic tool to screen for the disease. All these reports used the aspiration nNO method. The goal of this study was to evaluate nNO in patients with PCD using different methods of NO measurement, including continuous aspiration, silent exhalation, and single-breath humming exhalation, which increases NO wash-out from the paranasal sinuses to the nose. MATERIAL/METHODS: Fourteen patients with established diagnosis of PCD and 14 healthy controls (HC) were examined. Oral and nasal NO levels were measured by chemiluminescence. Each subject performed NO measurement in triplicate during oral exhalation, nasal aspiration (nNOasp), nasal exhalation (nNOexh), and single-breath humming (nNOhum). RESULTS: The median nNOasp value (95% confidence interval) was 11.6 (7.2-19.1) ppb in PCD and 321.8 (270.6-510.6) ppb in HC (p<0.001). The nNOexh value was 2.2 (1.3-3.1) in PCD and 31.8 (26.6-47.2) ppb in HC (p<0.001). Patients with PCD had lower nNO than HC during the last 80% of the exhalation throughout humming, i.e. 2.8 (2.2-4.3) ppb vs. 212.4 (158.7-244.8) ppb (p<0.001), and did not show a clear nNO peak. All nasal NO measurements had excellent specificity and sensitivity in detecting PCD compared with the healthy controls. CONCLUSIONS: nNO is consistently low in PCD with good specificity and sensitivity whatever the method used for NO measurement. The extremely low levels of nNO during humming support the notion that NO is defective in the paranasal sinuses in PCD.

Increased risk of chronic suppurative lung disease after measles or pertussis in non-vaccinated children.

We retrospectively analysed 23 children originating from Campania--Southern Italy--with recurrent pneumonia and chest high-resolution computed tomography (HRCT) proven bronchiectasis. In six patients (26%) who had not undergone measles or pertussis vaccination, recurrent pneumonia started after an episode of lower respiratory tract infection complicating pertussis (n=2) or measles (n=4), contracted at a mean age of 3.6 years. Thirty-three percent (2/6) and 67% (4/6) of the patients had bilateral or monolobar disease, respectively, while in two subjects (33%) bronchiectasis were found in all lobes. These findings indicate an increased risk of developing bronchiectasis after measles or pertussis.