Congenital respiratory tract disorders in 22q11.2 deletion syndrome.

OBJECTIVE: Respiratory tract disorders have been reported in patients with 22q11.2 deletion syndrome, however infrequently. This study describes the respiratory tract disorders encountered in a cohort of 278 patients with 22q11.2 deletion syndrome. METHODS: We conducted a retrospective, cross-sectional, study at a single tertiary referral center. We identified the patients with 22q11.2 deletion syndrome and with an upper and/or lower respiratory tract disorder at our otorhinolaryngologic department. The different disorders were described. RESULTS: Out of 278 patients referred to the otorhinolaryngologic department, we identified 14 patients with a laryngeal and/or tracheal disorder. Nine patients had more than one congenital disorder in this anatomical area. Disorders included a choanal stenosis (n = 1), laryngeal web (n = 5), laryngeal cleft (n = 2), subglottic stenosis (n = 3), pharyngo-, laryngo-, tracheo- and/or bronchomalacia (n = 11) and tracheal stenosis (n = 1). CONCLUSION: Different types of respiratory tract disorders can be present in patients with 22q11.2 deletion syndrome. Clinicians should be aware of this clinical association for timely and accurate diagnosis and treatment. In addition, the diagnosis 22q11.2 deletion syndrome should be considered in patients presenting with a congenital respiratory tract disorder.

Mutación CCDC103: una variante rara como causa de discinesia ciliar primaria / CCDC103 mutation: a rare variant as cause of primary ciliary dyskinesia

Introducción. La discinesia ciliar primaria (DCP) es un conjunto de enfermedades caracterizadas por una disfunción de las estructuras ciliadas del epitelio bronquial y gonadal. Puede deberse a que los cilios sean inmóviles, tengan un movimiento ineficaz o, menos frecuentemente, a la ausencia total de los mismos. Como consecuencia de esta disfunción se producen las manifestaciones clínicas: bronquiectasias, sinusitis crónica y, en ocasiones, esterilidad en los varones. Se trata de la segunda causa más frecuente de enfermedad congénita respiratoria, por detrás de la fibrosis quística, con una herencia autosómica recesiva. Actualmente se están intentando identificar y definir los genes y mutaciones causantes de la enfermedad. Paciente. Se presenta un caso de DCP asociada a situs inversus en el que el diagnóstico se estableció por estudio genético. Presentamos el caso por la singularidad de la sospecha diagnóstica desde el periodo neonatal, por haberse realizado el diagnóstico a los 2 años, 9 meses (antes que la edad media habitual) y por la escasa prevalencia de la variante encontrada en la población europea. Resultados. Se identifica en este caso, en homozigosis, una variante: c.461A>C (p.H154P) en el gen CCDC103 (NM-213607.2), rara, ya que se encuentra en un 0,1% de la población europea (AU)

Introduction. Primary ciliary dyskinesia (DCP) englobes a set of diseases in which the microscopic cells in the respiratory and gonadal system do not function normally. This dysfunction is produced by immotile cilia, abnormal movement or, less frequent, absence of cilia at all. This ciliary dysfunction produces the different clinic manifestations, such as: chronic sinusitis, bronchiectasis and sometimes infertility in men. It usually follows autosomal recessive genetic inheritance. The genes responsible of this disorder are actually being identified. Patient. We present a case of DCP asociated to situs inversus, in wich the diagnosis was established with genetic study. This is a singular case, because the diagnosis was done sooner than the medium age (2 years and 9 months old), it was also suspected in the neonatal period and the low prevalence of this variant. Results. Exome sequencing identified a homozygous missense variant in CCDC103 (C.461A>C, p.H154P). This is a rare variant which only occurs in approximately 0.1% of european population (AU)

Effect of low tidal volume with PEEP on respiratory function in infants undergoing one-lung ventilation.

BACKGROUND: An increasing number of studies have shown that low tidal volume (TV) with positive end-expiratory pressure (PEEP) offers lung protection during one-lung ventilation (OLV). Considering the unique physiological characteristics of infants, we aimed to determine the feasibility and effect of low TV with PEEP in infants undergoing OLV during thoracoscopy. PATIENTS AND METHODS: We randomized 60 infants to a conventional group (group I: TV, 8-10 ml/kg; RR, 23-45 bpm; PEEP, 0 cmH2O) or a low TV with PEEP group (group II: TV, 5-7 ml/kg; RR, 23-45 bpm; PEEP, 4-6 cmH2O). Arterial blood gas analyses were performed at four time points: 5 min of two-lung ventilation (TLV, T0), and 20 min, 40 min, and 60 min of OLV (T1, T2, T3); hemodynamic parameters (heart rate, mean blood pressure), temperature, as well as gas exchange (SpO2 and PETCO2) and ventilation parameters (FiO2, PEEP, Pmax) were recorded simultaneously. Lung compliance and shunt were also calculated. RESULT: No significant difference was found between both groups at T0. Compared with T0, PETCO2, Pmax, PaCO2, lactic acid, and intrapulmonary shunt volume (Qs/Qt) were increased while PaO2 and respiratory system compliance (Cdyx) were decreased noticeably in both groups at T1, T2, and T3. At T1, T2, and T3, Pmax and Qs/Qt were much lower while PETCO2, PaCO2, and Cdyx were higher in group II than in group I. There was no significant difference in lactic acid and PaO2 measurements between the two groups at T1, T2, and T3. CONCLUSION: Low TV with PEEP could be an effective intraoperative ventilation strategy for infants undergoing OLV during video-assisted thoracoscopic surgery and may reduce the risk of lung injury. However, this strategy, as well as the influence of intraoperative hypercapnia on infants, needs further investigation.

Association of airway abnormalities with 22q11.2 deletion syndrome.

INTRODUCTION: 22q11.2 deletion syndrome (22q11.2DS) presents with complex but variable symptoms, including cardiac, immune, palatal, endocrine, cognitive, and psychiatric issues. However, an association of 22q11.2DS with structural airway abnormalities has not been formally described. The aim of this study was to document the frequency of this association. METHODS: We retrospectively reviewed medical records of patients with 22q11.2DS evaluated in the 22q and You Center at the Children's Hospital of Philadelphia between 1999 and 2015 referred to otolaryngology for an airway assessment. Type of airway abnormality and presence of comorbidities, such as congenital heart disease, tracheostomy, and association with prenatal symptomatology such as polyhydramnios, were noted. RESULTS: Of the 104 patients who underwent an otolaryngology procedure (microlaryngoscopy or bronchoscopy), 71% (n = 74) had airway abnormalities. Patients with airway abnormalities ranged in age from 5 months to 37 years, with similar prevalence among males and females. Observed airway abnormalities included tracheomalacia (36%), subglottic stenosis (28%), laryngomalacia (26%), glottic web (21%), and bronchomalacia (16%). Most patients with airway abnormalities (91%) had an associated congenital heart defect, with ventricular septal defect and Tetralogy of Fallot being the most prevalent. Importantly, 30% of patients required a tracheostomy, and overall polyhydramnios was noted in 16% of pregnancies. CONCLUSION: Airway abnormalities are a common feature of 22q11.2DS, leading to substantial morbidity, particularly when combined with complex cardiac disease. Polyhydramnios may be an important prenatal clue to both the diagnosis of 22q11.2DS and airway anomalies. Postnatal assessment of airway structure and function among patients with 22q11.2DS is an important component of overall evaluation and will help guide long-term management.

Updates on MRI Evaluation of Pediatric Large Airways.

OBJECTIVE: The purposes of this article are to present a practical approach to imaging of common congenital and acquired diseases of the pediatric large airways with MRI and to describe the imaging findings. CONCLUSION: High-quality MRI of the airways is an increasingly feasible alternative to conventional radiography, fluoroscopy, and CT in the evaluation of many diseases of the pediatric large airways.

Hipertensión arterial pulmonar en cardiopatías congénitas con cortocircuito izquierda-derecha / Pulmonary arterial hypertension in congenital heart defects with left-to-right shunt

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Presence of tracheal bronchus in children undergoing flexible bronchoscopy.

BACKGROUND AND OBJECTIVES: Tracheal bronchus (TB) is a rare congenital malformation of the lung tree with a bronchus originating from the trachea. Only a small number of publications have analyzed the frequency and diagnostic procedure of TB in children, based on a restricted sample of patients. In the present study, we analyze and discuss new aspects of prevalence, clinical presentation and associated malformations of TB based on a large pediatric cohort. METHODS: Data from 5970 children having a flexible bronchoscopy for investigation of respiratory symptoms were selected. We analyzed the anaesthesic management, the presence of associated malformations, and all tracheobronchial anomalies observed during the endoscopic procedure. RESULTS: Fifty-seven cases of tracheal bronchus were identified (0.9%). In the majority of them, tracheal bronchus was a fortuitous discovery without clear clinical relevance. Statistical analysis revealed that the majority of TB originated from the middle and lower one third of the trachea (56%). 61.5% of patients had associated anomalies such as syndromic association (21%), cardiac malformations (19.2%) or tracheal stenosis (14%). Only 38.5% of children had no associated anomalies. CONCLUSIONS: Tracheal bronchus is a rare morphological anomaly of the tracheobronchial tree. Most often TB is associated with other birth defects such as another tracheo-bronchial tree malformation, vascular abnormality, congenital heart malformation or in the context of a syndromic pattern. A relationship between respiratory symptoms and the presence of TB is very rare and selective treatment is infrequent.

Cutis Laxa syndrome: a case report.

Cutis laxa (CL) is a heterogeneous group of inherited and acquired connective tissue disorders characterized by a loose skin and variable systemic involvement (inguinal hernia, cardiopulmonary disease, and emphysema). Autosomal dominant, autosomal recessive and x-linked recessive patterns have been described in the inherited forms. Acquired forms of this disease have been associated with a previous inflammatory skin disorder (urticaria…). The characteristic symptomatological pattern is resulting from paucity of elastic fibers. We report an 18 months old baby boy with a congenital cutis laxa. He was admitted in pediatric unit for respiratory disorders. The diagnosis of CL syndrome is based on clinical assessment of typical skin features and the associated extracutaneous finding.

Surfactant treatment for neonatal respiratory disorders other than respiratory distress syndrome.

BACKGROUND: It is suggested that there may be expanded use of surfactant replacement for the neonatal diseases such as meconium aspiration syndrome (MAS), pneumonia and possibly bronchopulmonary dysplasia (BPD). OBJECTIVE: To evaluate the characteristics and short-term outcome of the neonates given exogenous surfactant because of the diseases other than respiratory disease syndrome (RDS). METHODS: This retrospective study included 35 neonates admitted to the neonatal intensive care unit from January 2012 to December 2012 for an expanded use of surfactant. Data related to gestational age, birth weight, gender and perinatal risk factors were obtained from the patients' records. The short-term prognosis was also noted. RESULTS: The diagnosis was sepsis in 16 patients, eight MAS, seven transient tachypnea of the newborns (TTN) and four BPD. Mean gestational age was 35.6 ± 4.5 weeks and mean birth weight was 2661 ± 981 g. Of overall cases, 65% were boys and 35% girls. The mortality rate was 17%. Of six fatal cases, three was with BPD, two with sepsis and one with MAS. CONCLUSION: We think that surfactant replacement may be life saver in the neonatal diseases other than RDS such as BPD, MAS and sepsis by rapidly improving oxygenation. Further investigation is necessary to validate the significance of expanded use of surfactant.

Outcomes of tracheostomy in the neonatal intensive care unit: is there an optimal time?

OBJECTIVE: To compare short-term outcomes of infants who underwent early versus late tracheostomy during their initial hospitalization after birth and determine the association, if any, between tracheostomy timing and outcomes. STUDY DESIGN: Retrospective chart review of infants who underwent a tracheostomy during their initial hospitalization at a single site. RESULTS: The median (range) gestational age of our cohort (n = 127) was 28 (23-42) weeks and birth weight was 988 (390-4030) g. Tracheostomy indications included airway lesions (47%), bronchopulmonary dysplasia (25%), both (22%) and others (6%). Median postmenstrual age (PMA) at tracheostomy was 45 (35-75) weeks. Death occurred in 27 (21%) infants and 65 (51%) infants were mechanically ventilated. G-tube was present at discharge in 42 (33%) infants. Infants who underwent early tracheostomy (<45 weeks PMA) (n = 66) had significantly lower gestational ages, weights and respiratory support than the late (≥45 weeks PMA) (n = 61) group. Death (29.5% versus 14%), home ventilation (41% versus 21%) and G tube (44% versus 14%) were significantly more frequent in the late tracheostomy group. On bivariate regression, outcomes were not independently associated with tracheostomy timing, after adjustment for gestational age and respiratory support. CONCLUSIONS: Of infants who underwent tracheostomy during the initial hospitalization after birth, 21% died. On adjusted analysis, tracheostomy timing was not independently associated with outcomes.

Failure of the Laryngeal Mask Airway Unique™ and Classic™ in the pediatric surgical patient: a study of clinical predictors and outcomes.

BACKGROUND: Although predictors of laryngeal mask airway failure in adults have been elucidated, there remains a paucity of data regarding laryngeal mask airway failure in children. METHODS: The authors performed a retrospective database review of all pediatric patients who received a laryngeal mask anesthetic at their institution from 2006 to 2010. Device brands were restricted to LMA Unique™ (Cardinal Health, Dublin, OH) and LMA Classic™ (LMA North America, San Diego, CA), and primary outcome was laryngeal mask failure, defined as any airway event requiring device removal and tracheal intubation. Potential risk factors were analyzed with both univariate and multivariate techniques and included medical history, physical examination, surgical, and anesthetic characteristics. RESULTS: Of the 11,910 anesthesia cases performed in the study, 102 cases (0.86%) experienced laryngeal mask failure. Common presenting features of laryngeal mask failures included leak (25%), obstruction (48%), and patient intolerance such as intractable coughing/bucking (11%). Failures occurred before incision in 57% of cases and after incision in 43%. Independent clinical associations included ear/nose/throat surgical procedure, nonoutpatient admission status, prolonged surgical duration, congenital/acquired airway abnormality, and patient transport. CONCLUSIONS: The findings of the study support the use of the LMA Unique™ and LMA Classic™ as reliable pediatric supraglottic airway devices, demonstrating relatively low failure rates. Predictors of laryngeal mask airway failure in the pediatric surgical population do not overlap with those in the adult population and should therefore be independently considered.

Nongenital human papillomavirus disease.

Human papillomavirus (HPV) is the most common viral cause of cancer, and is responsible for 5% of cancers worldwide. Following demonstration of the causative link between HPV and cervical cancer, HPV has been shown to be associated with several anogenital malignancies and with oral pharyngeal cancers. HPV-related anal and oral pharyngeal disease is rising in incidence and includes anal warts and neoplasia, recurrent respiratory papillomatosis, and oral pharyngeal neoplasia. This article presents an overview of the epidemiology, clinical manifestations, diagnosis, and treatment of nongenital HPV-related disease.

Use of the Bonfils intubating fibrescope in a baby with a severely compromised airway.

We report the successful use of a 2-mm rigid Bonfils intubation endoscope as a rescue device in a 5-week-old baby presenting with an unstable airway due to massive macroglossia and multiple hemorrhagic lymphangiomata compressing the airway and resulting in a Cormack and Lehane grade 4 view. The limited intraoral space rendered it impossible to visualize the laryngeal inlet or insert a laryngeal mask, Glidescope or Airtraq blade into the patient's mouth. A 2-mm Bonfils fibrescope passed easily into the patient's mouth and facilitated a grade 1 view of the laryngeal inlet with subsequent successful intubation at first attempt with a 3.5-mm uncuffed endotracheal tube. There are very few alternatives to rescue such an airway in this age group with this type of pathology and surgical intervention would have been difficult due to the vascular nature of the lesion. Bonfils intubation endoscopes (Karl Storz Endoscopy, Tuttlingen, Germany) are a series of reusable devices consisting of a rigid metal tube with a fixed 40° anterior tip curvature containing a fibreoptic bundle. They are available in three sizes with outside diameters of 2, 3.5, or 5 mm. The advantage of the pediatric 2-mm Bonfils fibrescope is that it allows intubation with a 2.5-mm endotracheal tube. There is a paucity of the literature pertaining to the use of the Bonfils endoscope as a rescue device for intubation of small infants and neonates. In our case, the infant's airway was compromised as a result of a receding mandible, large protruding tongue, glottic distortion, and limited intraoral space. This prevented the use of bulkier rescue airway devices with the potential for traumatic manipulation, which could have lead to rapid deterioration of an already unstable airway. We feel that many clinicians are unaware of the benefits of the Bonfils fibrescope and suggest further studies to increase its use in elective and emergency situations.

Fetal chest ultrasound and magnetic resonance imaging: recent advances and current clinical applications.

Advances in high-resolution prenatal ultrasound and fetal magnetic resonance (MR) imaging have changed the practice of obstetrics by allowing better visualization of intrathoracic and neck structures and better estimation of lung volumes. More accurate prenatal diagnosis has increased options for pregnancy management and treatment, delivery planning, and postnatal care. Anyone who is interested in the fascinating field of fetology should become familiar with the current state of fetal imaging of the chest as well as potential advances in technology and research.

Multidetector computed tomography of pediatric large airway diseases: state-of-the-art.

Advances in multidetector computed tomography (MDCT) technology have given rise to improvements in the noninvasive and comprehensive assessment of the large airways in pediatric patients. Superb two-dimensional and three-dimensional reconstruction MDCT images have revolutionized the display of large airways and enhanced the ability to diagnose large airway diseases in children. The 320-MDCT scanner, which provides combined detailed anatomic and dynamic functional information assessment of the large airways, is promising for the assessment of dynamic large airway disease such as tracheobronchomalacia. This article discusses imaging techniques and clinical applications of MDCT for assessing large airway diseases in pediatric patients.

Developmental aspects of the upper airway: report from an NHLBI Workshop, March 5-6, 2009.

The upper airway serves three important functions: respiration, swallowing, and speech. During development it undergoes significant structural and functional changes that affect its size, shape, and mechanical properties. Abnormalities of the upper airway require prompt attention, because these often alter ventilatory patterns and gas exchange, particularly during sleep when upper airway motor tone and ventilatory drive are diminished. Recognizing the relationship of early life events to lung health and disease, the National Heart, Lung, and Blood Institute (NHLBI), with cofunding from the Office of Rare Diseases (ORD), convened a workshop of extramural experts, from many disciplines. The objective of the workshop was: (1) to review the state of science in pediatric upper airway disorders; (2) to make recommendations to the Institute to fill knowledge gaps; (3) to prioritize new research directions; and (4) to capitalize on scientific opportunities. This report provides recommendations that could facilitate translation of basic research findings into practice to better diagnose, treat, and prevent airway compromise in children.

Airway pathologic abnormalities in symptomatic children with congenital cardiac and vascular disease.

OBJECTIVE: To identify the epidemiological profile of airway abnormalities in symptomatic children with cardiac or vascular anomalies. DESIGN: Retrospective medical chart review. SETTING: Tertiary referral pediatric hospital. PATIENTS: Children with airway-related symptoms and coexistent cardiac or vascular abnormality were included. The source for patient identification was a prospectively kept database. MAIN OUTCOME MEASURES: Endoscopic airway diagnoses, presenting airway symptoms, cardiac diagnoses, other comorbid conditions and pertinent diagnoses, patient demographics, source of referral, treatments, and follow-up. RESULTS: The study population comprised 77 patients (45 male and 32 female; mean age, 18.2 months) treated between June 2002 and July 2006. Only 4 patients had no findings. The most common airway abnormality was laryngeal paralysis (n=32), followed by subglottic stenosis (n=18). Congenital and acquired lesions were equally encountered (n=70 and n=64, respectively). The most frequent presentation was intolerance to feed (n=51) (stridor and/or failure of extubation). Of the 77 patients, 32 (42%) required airway surgical intervention (open vs closed); 36 (47%) still require otolaryngologic follow-up; and 32 (42%) had a named syndrome or general multisystem condition. CONCLUSIONS: At least 3% of all children with cardiac disease will harbor airway problems. Laryngeal paralysis was the most common problem encountered. Given the successes achievable in treating children with complex cardiac abnormalities, attention should be paid to concomitant and consequential airway problems. Counseling processes should acknowledge the role of early otolaryngologic involvement.

Vascular abnormalities in mice deficient for the G protein-coupled receptor GPR4 that functions as a pH sensor.

GPR4 is a G protein-coupled receptor expressed in the vasculature, lung, kidney, and other tissues. In vitro ectopic overexpression studies implicated GPR4 in sensing extracellular pH changes leading to cyclic AMP (cAMP) production. To investigate its biological roles in vivo, we generated GPR4-deficient mice by homologous recombination. Whereas GPR4-null adult mice appeared phenotypically normal, neonates showed a higher frequency of perinatal mortality. The average litter size from GPR4(-/-) intercrosses was approximately 30% smaller than that from GPR4(+/+) intercrosses on N3 and N5 C57BL/6 genetic backgrounds. A fraction of knockout embryos and neonates had spontaneous hemorrhages, dilated and tortuous subcutaneous blood vessels, and defective vascular smooth muscle cell coverage. Mesangial cells in kidney glomeruli were also significantly reduced in GPR4-null neonates. Some neonates exhibited respiratory distress with airway lining cell metaplasia. To examine whether GPR4 is functionally involved in vascular pH sensing, an ex vivo aortic ring assay was used under defined pH conditions. Compared to wild-type aortas, microvessel outgrowth from GPR4-null aortas was less inhibited by acidic extracellular pH. Treatment with an analog of cAMP, a downstream effector of GPR4, abolished microvessel outgrowth bypassing the GPR4-knockout phenotype. These results suggest that GPR4 deficiency leads to partially penetrant vascular abnormalities during development and that this receptor functions in blood vessel pH sensing.

Infant morbidity following amniocentesis and chorionic villus sampling for prenatal karyotyping.

OBJECTIVE: To investigate whether amniocentesis and chorionic villus sampling increase the risk of postural deformities, limb reduction defects, respiratory problems in the newborn, fetal and infant mortality, prematurity, low birthweight and fetal distress, and to investigate the impact of gestational length at the time of the procedure. DESIGN: A population-based cohort study. SETTING: Sweden, 1991-1996. POPULATION: All women, 35 to 49 years old, with single births (n= 71,586). The women were classified as exposed to amniocentesis (n= 21,748) or chorionic villus sampling (n= 1984) or not exposed (n= 47,854). METHODS: Infant outcomes were collected from the Swedish Medical Birth Register, the Swedish Hospital Discharge Register, the Swedish Malformation Register and the Swedish Cause of Death Register. Odds ratios were calculated with logistic regression analyses. MAIN OUTCOME MEASURES: Crude and adjusted odds ratios of postural deformities, limb reduction defects, respiratory problems in the newborn, fetal and infant mortality, prematurity, low birthweight and fetal distress. Women exposed to amniocentesis or chorionic villus sampling were compared with non-exposed women. RESULTS: An increased risk of musculoskeletal deformities (OR = 1.32, 95% CI 1.11-1.57) including club foot and hip dislocation was found in the amniocentesis group, especially for amniocentesis prior to 14 weeks of gestation. Respiratory disturbances such as neonatal pneumonia, meconium aspiration, atelectasis and tachypnea were found more often in the amniocentesis group (OR = 1.12, 95% CI 1.02-1.24), with the greatest risk at 14 and 15 weeks of gestation. For the chorionic villus sampling group, no significant associations were found. No increase regarding limb reduction defects, fetal and infant mortality, prematurity, low birthweight and fetal distress was found in either the amniocentesis or the chorionic villus sampling group. CONCLUSIONS: Among women aged 35-49 years, amniocentesis before 14 weeks of gestation increases the risk of postural deformities. Amniocentesis at 14 and 15 weeks increases the risk of respiratory disturbances. For chorionic villus sampling, a larger study group is needed before such risks can be ruled out.