Montelukast in paediatric asthma and allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: We aim to assess the impact of montelukast on paediatric patients with asthma/allergic rhinitis, measured using patient-reported outcome measures, compared with other treatments or placebo. METHODS: Protocol registration CRD42020216098 (www.crd.york.ac.uk/PROSPERO). MEDLINE and Embase databases were used to conduct the search. Two authors independently selected studies and extracted data, and a third reviewer resolved discrepancies. Meta-analyses were constructed to estimate the standardised mean difference (SMD) using a random-effects model. RESULTS: Out of 3937 articles identified, 49 studies met the inclusion criteria, mostly randomised clinical trials (sample sizes: 21-689 patients). The SMD of change pooled estimators for the global, mental and physical domains of health-related quality of life were not statistically significant. For daytime and night-time symptoms scores, the SMD (95% CI) was in favour of inhaled corticosteroids (-0.12, -0.20- -0.05 and -0.23, -0.41- -0.06, respectively). The pooled estimator for global asthma symptoms was better for montelukast when compared with placebo (0.90, 0.44-1.36). CONCLUSIONS: The synthesis of the available evidence suggests that, in children and adolescents, montelukast was effective in controlling asthma symptoms when compared with placebo, but inhaled corticosteroids were superior in controlling symptoms, especially at night-time. These findings of our systematic review concur with current guidelines for asthma treatment.

Implementation of a Gene Panel for Genetic Diagnosis of Primary Ciliary Dyskinesia. / Implementación de un panel de genes para el diagnóstico genético de la discinesia ciliar primaria.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is characterized by an alteration in the ciliary structure causing difficulty in the clearance of respiratory secretions. Diagnosis is complex and based on a combination of techniques. The objective of this study was to design a gene panel including all known causative genes, and to corroborate their diagnostic utility in a cohort of Spanish patients. METHODS: This was a multicenter cross-sectional study of patients with a high suspicion of PCD, according to European Respiratory Society criteria, designed around a gene panel for massive sequencing using SeqCap EZ capture technology that included 44 genes associated with PCD. RESULTS: We included 79 patients, 53 of whom had a diagnosis of confirmed or highly probable PCD. The sensitivity of the gene panel was 81.1%, with a specificity of 100%. Candidate variants were found in some of the genes of the panel in 43 patients with PCD, 51.2% (22/43) of whom were homozygotes and 48.8% (21/43) compound heterozygotes. The most common causative genes were DNAH5 and CCDC39. We found 52 different variants, 36 of which were not previously described in the literature. CONCLUSIONS: The design and implementation of a tailored gene panel produces a high yield in the genetic diagnosis of PCD. This panel provides a better understanding of the causative factors involved in these patients and lays down the groundwork for future therapeutic approaches.

Immunofluorescence Analysis as a Diagnostic Tool in a Spanish Cohort of Patients with Suspected Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is an autosomal recessive rare disease caused by an alteration of ciliary structure. Immunofluorescence, consisting in the detection of the presence and distribution of cilia proteins in human respiratory cells by fluorescence, has been recently proposed as a technique to improve understanding of disease-causing genes and diagnosis rate in PCD. The objective of this study is to determine the accuracy of a panel of four fluorescently labeled antibodies (DNAH5, DNALI1, GAS8 and RSPH4A or RSPH9) as a PCD diagnostic tool in the absence of transmission electron microscopy analysis. The panel was tested in nasal brushing samples of 74 patients with clinical suspicion of PCD. Sixty-eight (91.9%) patients were evaluable for all tested antibodies. Thirty-three cases (44.6%) presented an absence or mislocation of protein in the ciliary axoneme (15 absent and 3 proximal distribution of DNAH5 in the ciliary axoneme, 3 absent DNAH5 and DNALI1, 7 absent DNALI1 and cytoplasmatic localization of GAS8, 1 absent GAS8, 3 absent RSPH9 and 1 absent RSPH4A). Fifteen patients had confirmed or highly likely PCD but normal immunofluorescence results (68.8% sensitivity and 100% specificity). In conclusion, immunofluorescence analysis is a quick, available, low-cost and reliable diagnostic test for PCD, although it cannot be used as a standalone test.

Primary ciliary dyskinesia: clinical criteria indicating ultrastructural studies.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a congenital disease characterized by impaired ciliary function, which involves a wide range of symptoms that are mainly respiratory. Recent articles that base diagnosis on ciliary ultrastructural studies have estimated its prevalence to be 1/10,000 newborns, which is higher than previously thought. Our objective is to define criteria for clinical suspicion of DCP that would indicate ultrastructural studies, while optimizing these and providing early diagnoses. METHODS: Ours is a descriptive, retrospective review of patients diagnosed with DCP in the Pediatric Pulmonology Unit at our hospital, from 1994 to 2010. The inclusion of cases was based on clinical suspicion criteria. Diagnosis was confirmed by characteristic ultrastructural changes observed in the electron microscopic study of the cilia. RESULTS: Sixty-three samples were analyzed, and 34 cases of DCP and one case of acilia were confirmed. Mean age at diagnosis was 3.6 (range: 1 month to 19 years of age). The most frequent initial symptom was prolonged neonatal tachypnea in the newborns (20%) and lower respiratory tract episodes in the school-aged patients: recurrent pneumonia (46%), difficult-to-control asthma (26%), bronchiectasis (8.6%) and massive atelectasis (2.9%). Associated symptoms were present in 46% of the cases. CONCLUSION: Our publication proposes the implementation of several clinical criteria depending on the age of presentation that would indicate the active search for alterations in the ciliary epithelium at reference centers.

Discinesia ciliar primaria: criterios clínicos de indicación de estudio ultraestructural / Primary Ciliary Dyskinesia: Clinical Criteria Indicating Ultrastructural Studies

Introducción: La discinesia ciliar primaria (DCP) es una enfermedad caracterizada por disfunción de las células ciliadas que se manifiesta con una sintomatología muy variable, principalmente respiratoria. Trabajos recientes que basan el diagnóstico en el estudio ultraestructural ciliar calculan una prevalencia mayor de la estimada previamente, situándola en 1/10.000 nacidos vivos. Nuestro objetivo es definir unos criterios clínicos de sospecha de DCP que sirvan de indicación para dicho estudio, lo que permitiría optimizarlo y realizar un diagnóstico precoz. Métodos: Revisión retrospectiva de los pacientes diagnosticados de DCP en la Unidad de Neumología Infantil del hospital entre 1994 y 2010. La inclusión de los casos se determinó a partir de criterios clínicos de sospecha. El diagnóstico se confirmó con la observación de cambios ultraestructurales característicos en el estudio ciliar por microscopia electrónica. Resultados: Se analizaron 63 muestras y se confirmaron 34 casos de DCP y un caso de acilia. La edad media del diagnóstico fue de 3,6 años (rango de un mes a 19 años). La clínica inicial más frecuente fue taquipnea neonatal prolongada en los recién nacidos (20%) y cuadros de vías respiratorias bajas en los pacientes en edad escolar: neumonías recurrentes (46%), asma de difícil control (26%), bronquiectasias (8,6%) y atelectasia masiva (2,9%). En el 46% de los casos existían síntomas asociados. Conclusiones: Se propone la aplicación de un determinado número de criterios clínicos dependiendo de la edad de presentación que indiquen la búsqueda activa de una alteración en el epitelio ciliar en centros de referencia(AU)

Introduction: Primary ciliary dyskinesia (PCD) is a congenital disease characterized by impaired ciliary function, which involves a wide range of symptoms that are mainly respiratory. Recent articles that base diagnosis on ciliary ultrastructural studies have estimated its prevalence to be 1/10000 newborns, which is higher than previously thought. Our objective is to define criteria for clinical suspicion of DCP that would indicate ultrastructural studies, while optimizing these and providing early diagnoses. Methods: Ours is a descriptive, retrospective review of patients diagnosed with DCP in the Pediatric Pulmonology Unit at our hospital, from 1994 to 2010. The inclusion of cases was based on clinical suspicion criteria. Diagnosis was confirmed by characteristic ultrastructural changes observed in the electron microscopic study of the cilia. Results: Sixty-three samples were analyzed, and 34 cases of DCP and 1 case of acilia were confirmed. Mean age at diagnosis was 3.6 (range: 1 month to 19 years of age). The most frequent initial symptom was prolonged neonatal tachypnea in the newborns (20%) and lower respiratory tract episodes in the school-aged patients: recurrent pneumonia (46%), difficult-to-control asthma (26%), bronchiectasis (8.6%) and massive atelectasis (2.9%). Associated symptoms were present in 46% of the cases. Conclusion: Our publication proposes the implementation of several clinical criteria depending on the age of presentation that would indicate the active search for alterations in the ciliary epithelium at reference centers(AU)