Lower airway clinical outcome measures for use in primary ciliary dyskinesia research: a scoping review.

OBJECTIVES: Disease-specific, well-defined and validated clinical outcome measures are essential in designing research studies. Poorly defined outcome measures hamper pooling of data and comparisons between studies. We aimed to identify and describe pulmonary outcome measures that could be used for follow-up of patients with primary ciliary dyskinesia (PCD). METHODS: We conducted a scoping review by systematically searching MEDLINE, Embase and the Cochrane Database of Systematic Reviews online databases for studies published from 1996 to 2020 that included ≥10 PCD adult and/or paediatric patients. RESULTS: We included 102 studies (7289 patients). 83 studies reported on spirometry, 11 on body plethysmography, 15 on multiple-breath washout, 36 on high-resolution computed tomography (HRCT), 57 on microbiology and 17 on health-related quality of life. Measurement and reporting of outcomes varied considerably between studies (e.g. different scoring systems for chest HRCT scans). Additionally, definitions of outcome measures varied (e.g. definition of chronic colonisation by respiratory pathogen), impeding direct comparisons of results. CONCLUSIONS: This review highlights the need for standardisation of measurements and reporting of outcome measures to enable comparisons between studies. Defining a core set of clinical outcome measures is necessary to ensure reproducibility of results and for use in future trials and prospective cohorts.

Pulmonary exacerbations in patients with primary ciliary dyskinesia: an expert consensus definition for use in clinical trials.

Pulmonary exacerbations are a cause of significant morbidity in patients with primary ciliary dyskinesia (PCD) and are frequently used as an outcome measure in clinical research into chronic lung diseases. So far, there has been no consensus on the definition of pulmonary exacerbations in PCD. 30 multidisciplinary experts and patients developed a consensus definition for children and adults with PCD. Following a systematic review, the panel used a modified Delphi process with a combination of face-to-face meetings and e-surveys to develop a definition that can be used in research settings for children and adults with PCD. A pulmonary exacerbation was defined by the presence of three or more of the following seven items: 1) increased cough, 2) change in sputum volume and/or colour, 3) increased shortness of breath perceived by the patient or parent, 4) decision to start or change antibiotic treatment because of perceived pulmonary symptoms, 5) malaise, tiredness, fatigue or lethargy, 6) new or increased haemoptysis, and 7) temperature >38°C. The consensus panel proposed that the definition should be used for future clinical trials. The definition should be validated and the usability assessed during these studies.

Cardiorespiratory sleep studies at home: experience in research and clinical cohorts.

OBJECTIVE: To evaluate the success rates of home cardiorespiratory polygraphy in children under investigation for sleep-disordered breathing and parent perspectives on equipment use at home. DESIGN: Prospective observational study. SETTING: Sheffield, Evelina London and Southampton Children's Hospitals. PATIENTS: Data are reported for 194 research participants with Down syndrome, aged 0.5-5.9 years across the three centres and 61 clinical patients aged 0.4-19.5 years from one centre, all of whom had home cardiorespiratory polygraphy including respiratory movements, nasal pressure flow, pulse oximetry, body position and motion. MAIN OUTCOME MEASURES: Percentage of home cardiorespiratory studies successfully acquiring ≥4 hours of artefact-free data at the first attempt. Parental report of ease of use of equipment and preparedness to repeat home diagnostics in the future. RESULTS: 143/194 (74%; 95% CI 67% to 79%) of research participants and 50/61 (82%; 95% CI 71% to 90%) of clinical patients had successful home cardiorespiratory polygraphy at the first attempt. Some children required multiple attempts to achieve a successful study. Overall, this equated to 1.3 studies per research participant and 1.2 studies per clinical child. The median artefact-free sleep time for successful research studies was 515 min (range 261-673) and for clinical studies 442 min (range 291-583). 84% of research and 87% of clinical parents expressed willingness to repeat home cardiorespiratory polygraphy in the future. 67% of research parents found the equipment 'easy or okay' to use, while 64% of clinical parents reported it as 'easy' or 'very easy'. CONCLUSIONS: Home cardiorespiratory polygraphy offers an acceptable approach to the assessment of sleep-disordered breathing in children.

The validity and acceptability of a text-based monitoring system for pediatric asthma studies.

A meaningful analysis in research requires robust, valid data. Paper diaries allow the collection of data from individuals over time but are notorious for poor compliance and validity. SMS-technology is a novel method for data collection in medical research. Time-tagged SMS are transferred directly to an electronic file. We used SMS to collect symptoms and peak flow rate (PEFR) meter readings from 32 children with asthma. Parents responded first to five SMS daily for 7 days during an asymptomatic period and then for 14 days during a cold. Compliance with use of PEFR meter and SMS system were assessed. Digital PEFR meters enabled data download at the end of the study to confirm validity of transmitted data. Parents of 24 participants provided feedback about this data collection tool. Mean (±SD) "SMS-diary and PEFR-meter compliance" were 96% (±8) and 84% (±21) during baseline and 91% (±12) and 82% (±20) during cold respectively. Correctly reported PEFR values were found in 65.5% of all cases, in 8.3% PEFR values sent were "self-invented" and 2.4% of values were missing. All of the 22 parents completing the baseline questionnaire were happy to use SMS for this study. Of the 20 parents completing the follow up questionnaire, 95% (19/20) found the system user-friendly, 55% (11/20) would be more likely to participate in studies if they were using SMS data collection and 25% (5/20) were "sometimes unhappy" about receiving messages. This real-time capture of data is well accepted and could avoid some of the pitfalls of backfilled paper diaries.

Metabolomics pilot study to identify volatile organic compound markers of childhood asthma in exhaled breath.

BACKGROUND: In-community non-invasive identification of asthma-specific volatile organic compounds (VOCs) in exhaled breath presents opportunities to characterize phenotypes, and monitor disease state and therapies. The feasibility of breath sampling with children and the preliminary identification of childhood asthma markers were studied. METHOD: End-tidal exhaled breath was sampled (2.5 dm³) from 11 children with asthma and 12 healthy children with an adaptive breath sampler. VOCs were collected onto a Tenax®/Carbotrap hydrophobic adsorbent trap, and analyzed by GC-MS. Classification was by retention-index and mass spectra in a 'breath matrix' followed by multivariate analysis. RESULTS: A panel of eight candidate markers (1-(methylsulfanyl)propane, ethylbenzene, 1,4-dichlorobenzene, 4-isopropenyl-1-methylcyclohexene, 2-octenal, octadecyne, 1-isopropyl-3-methylbenzene and 1,7-dimethylnaphtalene) were found to differentiate between the asthmatic and healthy children in the test cohort with complete separation by 2D principal components analysis (2D PCA). Furthermore, the breath sampling protocol was found to be acceptable to children and young people. CONCLUSION: This method was found to be acceptable for children, and healthy and asthmatic individuals were distinguished on the basis of eight VOCs at elevated levels in the breath of asthmatic children.

Unusual findings and diagnostic challenges in a child with Lemierre's disease.

16S rDNA polymerase chain reaction (PCR) in the diagnosis of fastidious organisms is becoming increasingly commonplace. We present the case of a child admitted to an acute paediatric unit of a university teaching hospital with otorrhoea, torticollis, and cervical lymphadenopathy. Examination revealed hepatosplenomegaly associated with pancytopenia. Radiological imaging confirmed a retropharyngeal abscess, bilateral mastoiditis, cerebellar lesions, and venous sinus thrombosis. Swabs of aural discharge grew anaerobes. Drainage of the retropharyngeal abscess and bilateral mastoidectomy were performed. Bone marrow aspiration was initially suspicious of acute leukaemia prompting further investigations, but cytogenetic analysis ruled out this diagnosis and changes were attributed to severe sepsis. Following 27 days of intravenous antibiotics and after clinical improvement, clindamycin was started. Intraoperative pus yielded no significant pathogens. A 16S rDNA PCR confirmed Fusobacterium necrophorum. The boy was discharged on a 6 week course of oral clindamycin.