Association between upper and lower respiratory disease among patients with primary ciliary dyskinesia: an international study.

Introduction: Nearly all patients with primary ciliary dyskinesia (PCD) report ear-nose-throat (ENT) symptoms. However, scarce evidence exists about how ENT symptoms relate to pulmonary disease in PCD. We explored possible associations between upper and lower respiratory disease among patients with PCD in a multicentre study. Methods: We included patients from the ENT Prospective International Cohort (EPIC-PCD). We studied associations of several reported ENT symptoms and chronic rhinosinusitis (defined using patient-reported information and examination findings) with reported sputum production and shortness of breath, using ordinal logistic regression. In a subgroup with available lung function results, we used linear regression to study associations of chronic rhinosinusitis and forced expiratory volume in 1 s (FEV1) accounting for relevant factors. Results: We included 457 patients (median age 15 years, interquartile range 10-24 years; 54% males). Shortness of breath associated with reported nasal symptoms and ear pain of any frequency, often or daily hearing problems, headache when bending down (OR 2.1, 95% CI 1.29-3.54) and chronic rhinosinusitis (OR 2.3, 95% CI 1.57-3.38) regardless of polyp presence. Sputum production associated with daily reported nasal (OR 2.2, 95% CI 1.20-4.09) and hearing (OR 2.0, 95% CI 1.10-3.64) problems and chronic rhinosinusitis (OR 2.1, 95% CI 1.48-3.07). We did not find any association between chronic rhinosinusitis and FEV1. Conclusion: Reported upper airway symptoms and signs of chronic rhinosinusitis associated with reported pulmonary symptoms, but not with lung function. Our results emphasise the assessment and management of upper and lower respiratory disease as a common, interdependent entity among patients with PCD.

Characteristics of Otologic Disease Among Patients With Primary Ciliary Dyskinesia.

Importance: Otologic disease is common among people with primary ciliary dyskinesia (PCD), yet little is known about its spectrum and severity. Objective: To characterize otologic disease among participants with PCD using data from the Ear-Nose-Throat Prospective International Cohort. Design, Setting, and Participants: This cross-sectional analysis of baseline cohort data from February 2020 through July 2022 included participants from 12 specialized centers in 10 countries. Children and adults with PCD diagnoses; routine ear, nose, and throat examinations; and completed symptom questionnaires at the same visit or within 2 weeks were prospectively included. Exposures: Potential risk factors associated with increased risk of ear disease. Main Outcomes and Measures: The prevalence and characteristics of patient-reported otologic symptoms and findings from otologic examinations, including potential factors associated with increased risk of ear inflammation and hearing impairment. Results: A total of 397 individuals were eligible to participate in this study (median [range] age, 15.2 [0.2-72.4] years; 186 (47%) female). Of the included participants, 204 (51%) reported ear pain, 110 (28%) reported ear discharge, and 183 (46%) reported hearing problems. Adults reported ear pain and hearing problems more frequently when compared with children. Otitis media with effusion-usually bilateral-was the most common otoscopic finding among 121 of 384 (32%) participants. Retracted tympanic membrane and tympanic sclerosis were more commonly seen among adults. Tympanometry was performed for 216 participants and showed pathologic type B results for 114 (53%). Audiometry was performed for 273 participants and showed hearing impairment in at least 1 ear, most commonly mild. Season of visit was the strongest risk factor for problems associated with ear inflammation (autumn vs spring: odds ratio, 2.40; 95% CI, 1.51-3.81) and age 30 years and older for hearing impairment (41-50 years vs ≤10 years: odds ratio, 3.33; 95% CI, 1.12-9.91). Conclusion and Relevance: In this cross-sectional study, many people with PCD experienced ear problems, yet frequency varied, highlighting disease expression differences and possible clinical phenotypes. Understanding differences in otologic disease expression and progression during lifetime may inform clinical decisions about follow-up and medical care. Multidisciplinary PCD management should be recommended, including regular otologic assessments for all ages, even without specific complaints.

Sinonasal disease among patients with primary ciliary dyskinesia: an international study.

Background: Sinonasal symptoms are a common feature of primary ciliary dyskinesia (PCD); however, literature about their severity and frequency, particularly during the life course, is scarce. Using baseline data from the Ear, nose and throat (ENT) Prospective International Cohort of PCD patients, we describe sinonasal disease in PCD. Methods: We included participants who had a routine sinonasal examination during which they completed a symptoms questionnaire. We compared frequency of reported symptoms and examination findings among children and adults, and identified characteristics potentially associated with higher risk of sinonasal disease using ordinal regression. Results: 12 centres contributed 384 participants; median age was 16 years (IQR 9-22), and 54% were male. Chronic nasal problems were the most common feature, reported by 341 (89%). More adults (33; 24%) than children (10; 4%) described hyposmia. Quality of life was moderately affected by rhinosinusitis among 136 participants with completed SNOT-22 questionnaires (median score 31; IQR 23-45). Examinations revealed nasal polyps among 51 of 345 participants (15%) and hypertrophic inferior nasal turbinates among 127 of 341 participants (37%). Facial pain was detected in 50 of 342 participants (15%). Nasal polyps, hypertrophic turbinates, deviated septum and facial pain were found more commonly in adults than children. The only characteristic associated with higher risk of sinonasal disease was age 10 years and older. Conclusions: Based on our findings, regular sinonasal examinations are relevant for patients with PCD of all ages. There is a need for improved management of sinonasal disease supported by evidence-based guidelines.

A core outcome set for research on the management of otitis media with effusion in otherwise-healthy children.

INTRODUCTION: A Core Outcome Set (COS) is an agreed list of outcome domains to be reported by all studies investigating a condition. A COS for Otitis Media with Effusion (OME) in children with cleft palate exists (called MOMENT), but there isn't one for otherwise-healthy children. This study investigates whether the MOMENT COS could also be applicable to otherwise-healthy children. METHODS: A long list of potential outcomes was generated (independently of MOMENT) via three methods: literature review to establish which outcomes are reported by OME studies, a review of outcomes contained in OME questionnaires, and a focus group asking parents of children with OME what matters to them. The long list drawn up using these sources identified no outcomes additional to ones in the MOMENT long list. An online questionnaire was subsequently undertaken, asking parents/guardians and professionals/researchers whether they think that the MOMENT final list outcomes would also be applicable to otherwise healthy children. RESULTS: A total of 134 people took part: 53 parents/guardians (recruited through UK NHS hospitals) and 81 professionals/researchers (recruited internationally). Overall, 128 (95.5%) agreed that the MOMENT outcomes can also apply to otherwise healthy children (100% parents/guardians, 92.6% professionals/researchers). CONCLUSIONS: The outcome domains identified in the COS for OME management in children with cleft palate can also be used in otherwise-healthy children.

Non-selective laryngeal reinnervation in a child with unilateral left vocal fold palsy utilizing laryngeal electromyography.

INTRODUCTION: The impact of unilateral vocal fold palsy (UVFP) on quality of life cannot be underestimated. Management may be complicated by difficulty in determining prognosis. Currently, there is no standardized management pathway for UVFP. Surgery is considered when speech and language therapy has not been successful or when there is significant aspiration and dysphonia. Surgical options for UVFP include injection laryngoplasty, thyroplasty and laryngeal reinnervation. METHODS: We report the case of a 6-year-old girl with a left UVFP sustained following PDA ligation. She suffered significant voice issues, aspiration and intermittent stridor limiting activities. Following multidisciplinary team reassessment including videofluoroscopy and perceptual and objective voice measures, laryngotracheobronchoscopy (LTB) and laryngeal electromyography (LEMG) with injection of Radiesse into the left vocal fold was undertaken. Consequently, she underwent non-selective laryngeal reinnervation with the aim of providing a permanent solution by the formation of an anastomosis between the ansa cervicalis and the main stump of the recurrent laryngeal nerve (RLN) resulting in improved muscle tone. RESULTS: LEMG indicated no spontaneous recovery. The laryngeal injection allowed for temporary improvement of voice and feeding. Consequently non-selective left laryngeal reinnervation using ansa cervicalis and repeat vocal cord injection was performed. Twelve months following surgery her voice remain greatly improved and there are no feeding issues or aspiration. CONCLUSION: In this case so far the use of LEMG and laryngeal reinnervation has proved successful. Non-selective laryngeal reinnervation techniques for UVFP may provide a permanent solution and should be considered in children as a management option in suitable cases.

The acceptability and tolerability of nasal douching in children with allergic rhinitis: A systematic review.

BACKGROUND: Allergic rhinitis (AR) is a significant issue in children. Treatment options include allergen avoidance, pharmacotherapy and immunotherapy. The use of nasal saline douching (NSD) in children has recently gained acceptability. However, there is limited data regarding the acceptability and tolerability of NSD in children with AR. METHODS: A search was conducted using Medline and Embase databases from January 1946 until June 2015 on the use of NSD in children aged 4-12 years with AR. All publications identified that assessed the beneficial effects, acceptability and tolerability were included. RESULTS: 40 studies were analyzed. Data varied considerably in terms of saline solutions used, modality of application, participant numbers, study design, follow up and outcomes. Factors that appear to influence the acceptability and tolerability of NSD include parental and health professionals' preconceptions, and characteristics of the solution. CONCLUSIONS: Nasal saline douching appears to be effective, being accepted and tolerated in the majority of children (78-100%). NSD has a significant positive impact on the quality of life in children with allergic rhinitis. When used as an adjunctive treatment having mainly a cleansing property, NSD potentiates the effects and may reduce the dose required of AR medications. Among the principal factors that influence the acceptability and tolerability of NSD are the child's age, delivery system and method, and tonicity. Nasal saline douching provides an accessible, low cost, low morbidity, easy to use treatment in children with allergic rhinitis.

Unresolved drooling in a previously healthy child caused by a brainstem malignancy.

Drooling occurs commonly in children below the age of two. In a small group of children this persists and an otorhinolaryngology consultation is sought. In children with no neurological abnormality or comorbidity, reassurance and behavioural management is often suggested. We present a case where drooling was the presenting feature of brain stem malignancy. Diagnosis was suggested following a sleep study demonstrating central apnoeas. Magnetic resonance imaging (MRI) showed an intra-axial brainstem tumour. This case highlights the importance of multidisciplinary team (MDT) management of children with persistent drooling of unknown cause.

A novel insight into the immunologic basis of chronic granulomatous invasive fungal rhinosinusitis.

BACKGROUND: Chronic granulomatous invasive fungal rhinosinusitis (CGIFRS) is a rare disease. The underlying immune responses that drive the development of CGIFRS, as opposed to successful pathogen clearance and controlled inflammation, are not currently known. OBJECTIVE: To characterize the immune responses associated with CGIFRS. METHODS: In addition to a battery of basic investigations, more in-depth immunologic testing involves ex vivo whole-blood stimulation with the polyclonal T-cell mitogen phytohemagglutinin and fungal antigens with interleukin (IL) 12, was undertaken to investigate cell-mediated immune responses associated with CGIFRS. RESULTS: Ex vivo whole-blood stimulation with the polyclonal T-cell mitogen phytohemagglutinin and fungal antigens with IL-12 identified reduced interferon gamma and increased IL-17A levels within the supernatant, which indicated increased in vivo T-helper (Th)17 responses and impaired Th1 responses compared with healthy controls. CONCLUSION: These findings suggest that the development of CGIFRS may be associated with an abnormally exaggerated host Th17 response, which caused failure to clear the fungal pathogen with refractory fungal infection of mucosal membranes, resulting in chronic tissue inflammation.

Treatment of severe tracheobronchomalacia: Ten-year experience.

INTRODUCTION: Paediatric tracheobronchomalacia is a rare but potentially serious condition. Severe tracheobronchomalacia requires intervention or operation. This is an evaluation of a ten-year experience at an institution. METHODS: In this retrospective study all patients were included that required an intervention for severe tracheobronchomalacia from 2003 to 2012. Symptoms, aetiology, comorbidities, localisation of the malacia, age at diagnosis, therapeutic measures and associated complications were evaluated. RESULTS: Forty-four patients with severe tracheobronchomalacia underwent intervention/operation. The predominant aetiology was vascular compression in 48%. The majority of patients had complex comorbidities, most importantly cardiac pathology in 66%. The median age at diagnosis was 3 months. A total of 17 aortopexies, 21 tracheostomies and 25 stent placements were performed. The mean follow-up was 2.6 years. Severe complications occurred in 12 patients. The most common complications were stent obstruction/fracture and tracheostomy tube obstruction. CONCLUSION: The management of severe tracheobronchomalacia is complex and the population of patients is very heterogeneous. Therefore the treatment has to be adapted for each patient individually. The decision strategies are discussed in this article. The surgical techniques for placement and safe removal of expandable bare metallic stents employed in our institution are presented. A multidisciplinary team of ENT surgeons, Intensivists, Cardiologists and Cardiac surgeons is of great importance.

Low Concentrations of Nitric Oxide Modulate Streptococcus pneumoniae Biofilm Metabolism and Antibiotic Tolerance.

Streptococcus pneumoniaeis one of the key pathogens responsible for otitis media (OM), the most common infection in children and the largest cause of childhood antibiotic prescription. Novel therapeutic strategies that reduce the overall antibiotic consumption due to OM are required because, although widespread pneumococcal conjugate immunization has controlled invasive pneumococcal disease, overall OM incidence has not decreased. Biofilm formation represents an important phenotype contributing to the antibiotic tolerance and persistence ofS. pneumoniaein chronic or recurrent OM. We investigated the treatment of pneumococcal biofilms with nitric oxide (NO), an endogenous signaling molecule and therapeutic agent that has been demonstrated to trigger biofilm dispersal in other bacterial species. We hypothesized that addition of low concentrations of NO to pneumococcal biofilms would improve antibiotic efficacy and that higher concentrations exert direct antibacterial effects. Unlike in many other bacterial species, low concentrations of NO did not result inS. pneumoniaebiofilm dispersal. Instead, treatment of bothin vitrobiofilms andex vivoadenoid tissue samples (a reservoir forS. pneumoniaebiofilms) with low concentrations of NO enhanced pneumococcal killing when combined with amoxicillin-clavulanic acid, an antibiotic commonly used to treat chronic OM. Quantitative proteomic analysis using iTRAQ (isobaric tag for relative and absolute quantitation) identified 13 proteins that were differentially expressed following low-concentration NO treatment, 85% of which function in metabolism or translation. Treatment with low-concentration NO, therefore, appears to modulate pneumococcal metabolism and may represent a novel therapeutic approach to reduce antibiotic tolerance in pneumococcal biofilms.

A simple closure technique for reversal of tracheoesophageal puncture.

Speech restoration after total laryngectomy has been revolutionized by the technique of tracheoesophageal puncture (TEP) and speech valve prosthesis placement. Unfortunately, complications may arise from this procedure, sometimes necessitating reversal and surgical closure of the TEP. We present a simple yet effective method of closing a TEP and review previously described techniques.