Grey scale texture analysis of endobronchial ultrasound mini probe images for prediction of benign or malignant aetiology.

BACKGROUND AND OBJECTIVE: Expert analysis of endobronchial ultrasound mini probe (EBUS-MP) images has established subjective criteria for discriminating benign and malignant disease. Minimal data are available for objective analysis of these images. The aim of this study was to determine if greyscale texture analysis could differentiate between benign and malignant lung lesions. METHODS: Digital EBUS-MP images with a gain setting of 10/19 and contrast setting of 4/8 from 2007 until 2012 inclusive were included. These images had an expert-defined region of interest (ROI) mapped. ROI were analysed for the following greyscale texture features: mean pixel value, difference between maximum and minimum pixel value, standard deviation of the mean pixel value, entropy, correlation, energy and homogeneity. Significant greyscale texture features differentiating benign from malignant disease were used by two physicians to assess a validation set. RESULTS: A total of 167 images were available. The first 85 lesions were used in the prediction set. Benign lesions had larger differences between maximum and minimum pixel values, larger standard deviations of the mean pixel values and higher entropy than malignant lesions (P < 0.0001 for all values). A total of 82 peripheral lesions were in the validation set. Physician 1 correctly classified 63/82 (76.8%) with a negative predictive value (NPV) for malignancy of 82% and positive predictive value (PPV) of 75%. Physician 2 correctly classified 62/82 (75.6%) with a NPV of 100% and PPV of 71.0%. CONCLUSIONS: Greyscale texture analysis of EBUS-MP images can help establish aetiology with a high NPV for malignancy.

Clinical utility of elective paediatric flexible bronchoscopy and impact on the quality of life: protocol for a single-centre, single-blind, randomised controlled trial.

INTRODUCTION: Elective flexible bronchoscopy (FB) is now widely available and standard practice for a variety of indications in children with respiratory conditions. However, there are no randomised controlled trials (RCTs) that have examined its benefits (or otherwise).Our primary aim is to determine the impact of FB on the parent-proxy quality-of-life (QoL) scores. Our secondary aims are to determine if undertaking FB leads to (a) change in management and (b) improvement of other relevant patient-reported outcome measures (PROMs). We also quantified the benefits of elective FB (using 10-point Likert scale). We hypothesised that undertaking elective FB will contribute to accurate diagnosis and therefore appropriate treatment, which will in turn improve QoL and will be deemed to be beneficial from patient and doctor perspectives. METHODS AND ANALYSIS: Our parallel single-centre, single-blind RCT (commenced in May 2020) has a planned sample size of 114 children (aged <18 years) recruited from respiratory clinics at Queensland Children's Hospital, Brisbane, Australia. Children are randomised (1:1 concealed allocation) within two strata: age (≤2 vs >2 years) and indication for FB (chronic cough vs other indications) to either (a) early arm (intervention where FB undertaken within 2 weeks) or (b) delayed (control, FB undertaken at usual wait time). Our primary outcome is the difference between groups in their change in QoL at the T2 timepoint when the intervention group has had the FB and the control group has not. Our secondary outcomes are change in management, change in PROMs, adverse events and the Likert scales. ETHICS AND DISSEMINATION: The human research ethics committee of the Queensland Children's Hospital granted ethical clearance (HREC/20/QCHQ/62394). Our RCT is conducted in accordance with Good Clinical Practice and the Australian legislation. Results will be disseminated through conference presentations, teaching avenues, workshops, websites and publications. REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12620000610932.

The utility of elective flexible bronchoscopy to improve quality of life and clinical outcomes for children: A systematic review.

INTRODUCTION: Elective flexible bronchoscopy (FB) is now widely available and standard practice for a variety of indications in children with respiratory conditions. However, there is limited evidence regarding the utility of elective FB in children. This systematic review (SRs) aimed to determine the utility of FB on its impact in clinical decision making and quality of life (QoL). METHODS: We searched Pubmed, Cochrane central register of controlled trials, Embase, World Health Organization Clinical Trials Registry Platform and Cochrane database of SRs from inception to April 20, 2023. We included SRs and randomized controlled trials (RCTs) that used parallel group design (comparing use of elective FB vs. no FB, or a wait-list approach [early FB vs. usual wait FB]) in children aged ≤ 18 years. Our protocol was prospectively registered and used Cochrane methodology for systemic reviews of interventions. RESULTS: Our search identified 859 articles; 102 duplicates were removed, and 753 articles were excluded by title and abstract. Four full text articles were reviewed and subsequently excluded, as none met the inclusion criteria outlined in our patient, intervention, comparator, outcome measures framework. CONCLUSIONS: There is a paucity of high-quality RCT evidence to support the routine use of elective FB in children with respiratory conditions. However, available retrospective and a single prospective study demonstrate the high utility of FB in the elective pediatric setting. REGISTRATION: PROSPERO CRD42021291305.

Phenotypic Features of Pediatric Bronchiectasis Exacerbations Associated With Symptom Resolution After 14 Days of Oral Antibiotic Treatment.

BACKGROUND: Respiratory exacerbations in children and adolescents with bronchiectasis are treated with antibiotics. However, antibiotics can have variable interindividual effects when treating exacerbations. RESEARCH QUESTION: Can phenotypic features associated with symptom resolution after a 14-day course of oral antibiotics for a nonsevere exacerbation of bronchiectasis be identified? STUDY DESIGN AND METHODS: Combining data from two multicenter randomized controlled trials, we identified 217 children with bronchiectasis assigned to at least 14 days of oral antibiotics to treat nonsevere (nonhospitalized) exacerbations. Univariable and then multivariable logistic regression were used to identify factors associated with symptom resolution within 14 days of commencing antibiotics. Identified associations were re-evaluated by mediation analysis. RESULTS: Of the 217 study participants (52% male patients), 41% were Indigenous (Australian First Nations, New Zealand Maori, or Pacific Islander). The median age was 6.6 years (interquartile range, 4.0-10.1 years). By day 14, symptoms had resolved in 130 children (responders), but persisted in the remaining 87 children (nonresponders). Multivariable analysis found those who were Indigenous (adjusted OR [AOR], 3.59; 95% CI, 1.35-9.54) or showed new abnormal auscultatory findings (AOR, 3.85; 95% CI, 1.56-9.52) were more likely to be responders, whereas those with multiple bronchiectatic lobes at diagnosis (AOR, 0.66; 95% CI, 0.46-0.95) or higher cough scores when starting exacerbation treatment (AOR, 0.55; 95% CI, 0.34-0.90) were more likely to be nonresponders. Detecting a respiratory virus at the beginning of an exacerbation was not associated with antibiotic failure at 14 days. INTERPRETATION: Children with Indigenous ethnicity, milder bronchiectasis, mild exacerbations (low reported cough scores), or new abnormal auscultatory signs are more likely to respond to appropriate oral antibiotics than those without these features. These patient and exacerbation phenotypes may assist clinical management and development of biomarkers to identify those whose symptoms are more likely to resolve after 14 days of oral antibiotics. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry; Nos.: ACTRN12612000011886 and ACTRN12612000010897; URL: https://www.anzctr.org.au.

An Automated Broncho-Arterial (BA) Pair Segmentation Process and Assessment of BA Ratios in Children with Bronchiectasis Using Lung HRCT Scans: A Pilot Study.

Bronchiectasis in children can progress to a severe lung condition if not diagnosed and treated early. The radiological diagnostic criteria for the diagnosis of bronchiectasis is an increased broncho-arterial (BA) ratio. From high-resolution computed tomography (HRCT) scans, the BA pairs must be detected first to derive the BA ratio. This study aims to identify potential BA pairs from HRCT scans of children undertaken to evaluate suppurative lung disease through an automated approach. After segmenting the lung regions, the HRCT scans are cleaned using a histogram analysis-based approach followed by a potential arteries identification process comprising four conditions based on imaging features. Potential arteries and their connected components are extracted, and potential bronchi are identified. Finally, the coordinates of potential arteries and potential bronchi are matched as the last step of BA pairs extraction. A total of 8-50 BA pairs are detected for each patient. Additionally, the area and several diameters of the bronchi and arteries are measured, and BA ratios based on these are calculated. Through this approach, the BA pairs of a CT scan datasets are detected and utilizing a deep learning model, a high classification test accuracy of 98.53% is achieved, validating the robustness of the proposed BA detection approach. The results show that visible BA pairs can be identified and segmented automatically, and the BA ratio calculated may help diagnose bronchiectasis with less effort and time.

Randomised controlled trial of amoxycillin clavulanate in children with chronic wet cough.

BACKGROUND: Despite guideline recommendations, there are no published randomised controlled trial data on the efficacy of antibiotics for chronic wet cough in children. The majority of children with chronic wet cough have protracted bacterial bronchitis (PBB), a recognised condition in multiple national guidelines. The authors conducted a parallel 1:1 placebo randomised controlled trial to test the hypothesis that a 2-week course of amoxycillin clavulanate is efficacious in the treatment of children with chronic wet cough. METHODS: 50 children (median age 1.9 years, IQR 0.9-5.1) with chronic (>3 weeks) wet cough were randomised to 2 weeks of twice daily oral amoxycillin clavulanate (22.5 mg/kg/dose) or placebo. The primary outcome was 'cough resolution' defined as a >75% reduction in the validated verbal category descriptive cough score within 14 days of treatment compared with baseline scores, or cessation of cough for >3 days. In selected children, flexible bronchoscopy and bronchoalveolar lavage (BAL) were undertaken at baseline. RESULTS: Cough resolution rates (48%) were significantly higher in children who received amoxycillin clavulanate compared with those who received placebo (16%), p=0.016. The observed difference between proportions was 0.32 (95% CI 0.08 to 0.56). Post treatment, median verbal category descriptive score in the amoxycillin clavulanate group of 0.5 (IQR 0.0-2.0) was significantly lower than in the placebo group, 2.25 (IQR 1.15-2.9) (p=0.02). Pre-treatment BAL data were consistent with PBB in the majority of children, with no significant difference between groups. CONCLUSION: A 2-week course of amoxycillin clavulanate will achieve cough resolution in a significant number of children with chronic wet cough. BAL data support the diagnosis of PBB in the majority of these children. CLINICAL TRIAL NUMBER: ACTRN 12605000533695.

Hemoglobin I-Toulouse: A rare hemoglobinopathy presenting with low oxygen saturations.

We report a child with persistently low oxygen saturations (SpO2 90%-92%) [normal SpO2 > 98%], with delayed diagnosis due to the co-existing congenital pulmonary airway malformation with possible arterio-venous malformation. The diagnosis was only achieved after low oxygen saturations incidentally discovered from the child's father. The eventual cause was Hemoglobin I-Toulouse, making both patients the first reported cases with low oxygen saturations.

Flexible Bronchoscopy Diagnosis of Uncommon Congenital H-type Tracheoesophageal Fistula, Dual Fistulae, Bronchoesophageal Fistula, and Recurrence of Fistula in Children: A 20-year Experience.

BACKGROUND: Interventional pediatric flexible bronchoscopy has many advantages over radiologic investigations in diagnosing uncommon congenital H-type tracheoesophageal fistula (TEF), dual TEF, bronchoesophageal fistula (BEF) and fistula recurrence including higher rates of identification and anatomic localization with guide wire cannulation. We compare the diagnostic utility of flexible bronchoscopy to radiologic techniques for congenital aerodigestive fistula. METHODS: A single center retrospective review was completed of all cases of pediatric TEF and BEF diagnosed with flexible bronchoscopy between January 2000 and November 2020. RESULTS: Fistulae were diagnosed 21 times in 18 patients at a median age of 1.22 years (interquartile range: 0.50 to 2.99). The median time from diagnosis to repair was 17.5 days (interquartile range: 5.5 to 43). Symptoms commonly related to fistula were found in all patients. Uncommon fistulae included single H-type TEF (n=10, 47.6%), dual H-type TEF (n=2, 9.5%), dual proximal and distal TEF with esophageal atresia (n=5, 23.8%), TEF recurrence (n=2, 14.3%), BEF (n=1, 4.8%), and a BEF recurrence (n=1, 4.8%). Flexible bronchoscopy confirmed the diagnosis in all fistulae using a guide wire cannulation or methylene blue dye injection. A combined procedure with simultaneous bronchoscopy and esophagoscopy was used for 6 fistulae. The positive examination rate was 75% for bronchoscopy compared with 2.6% for contrast swallow studies and 28.6% for tube esophagograms. CONCLUSIONS: Flexible bronchoscopy should be considered as a first line investigation in uncommon aerodigestive fistulae. In the absence of a skilled bronchoscopist, the best radiologic investigation is a pull-back tube esophagogram but may still require endoscopic confirmation at the time of fistula repair.

Association of childhood tracheomalacia with bronchiectasis: a case-control study.

OBJECTIVE: Children with tracheomalacia can develop chronic lower airway infection and neutrophilic inflammation. It is plausible children with tracheomalacia are at increased risk of developing bronchiectasis. We hypothesised that compared with controls, tracheomalacia in children is associated with bronchiectasis. DESIGN: Single-centre, case-control study. SETTING AND PATIENTS: 45 children with chest high-resolution CT (c-HRCT) confirmed bronchiectasis (cases) and enrolled in the Australian Bronchiectasis Registry were selected randomly from Queensland, and 90 unmatched children without chronic respiratory symptoms or radiographic evidence of bronchiectasis (disease controls). Cases and controls had flexible bronchoscopy performed for clinical reasons within 4 weeks of their c-HRCT. INTERVENTIONS: The bronchoscopy videos were reviewed in a blinded manner for: (a) any tracheomalacia (any shape deformity of the trachea at end-expiration) and (b) tracheomalacia defined by the European Respiratory Society (ERS) statement (>50% expiratory reduction in the cross-sectional luminal area). MAIN OUTCOME MEASURES AND RESULTS: Cases were younger (median age=2.6 years, IQR 1.5-4.1) than controls (7.8 years, IQR 3.4-12.8), but well-balanced for sex (56% and 52% male, respectively). Using multivariable analysis (adjusted for age), the presence of any tracheomalacia was significantly associated with bronchiectasis (adjusted OR (ORadj)=13.2, 95% CI 3.2 to 55), while that for ERS-defined tracheomalacia further increased this risk (ORadj=24.4, 95% CI 3.4 to infinity). CONCLUSION: Bronchoscopic-defined tracheomalacia is associated with childhood bronchiectasis. While causality cannot be inferred, children with tracheomalacia should be monitored for chronic (>4 weeks) wet cough, the most common symptom of bronchiectasis, which if present should be treated and then investigated if the cough persists or is recurrent.

Impact of using spirometry on clinical decision making and quality of life in children: protocol for a single centre randomised controlled trial.

INTRODUCTION: Although spirometry has been available for decades, it is underused in paediatric practice, other than in specialist clinics. This is unsurprising as there is limited evidence on the benefit of routine spirometry in improving clinical decision making and/or outcomes for children. We hypothesised that using spirometry for children being evaluated for respiratory diseases impacts on clinical decision making and/or improves patient-related outcome measures (PROMs) and/or quality of life (QoL), compared with not using spirometry. METHODS AND ANALYSIS: We are undertaking a randomised controlled trial (commenced in March 2020) that will include 106 children (aged 4-18 years) recruited from respiratory clinics at Queensland Children's Hospital, Australia. Inclusion criteria are able to perform reliable spirometry and a parent/guardian who can complete questionnaire(s). Children (1:1 allocation) are randomised to clinical medical review with spirometry (intervention group) or without spirometry (control group) within strata of consultation status (new/review), and cough condition (present/absent). The primary outcome is change in clinical decision making. The secondary outcomes are change in PROM scores, opinions regarding spirometry and degree of diagnosis certainty. Intergroup differences of these outcomes will be determined by χ2 test or unpaired t-test (or Mann-Whitney if not normally distributed). Change in outcomes within the control group after review of spirometry will also be assessed by McNemar's test or paired t-test/Wilcoxon signed-rank test. ETHICS AND DISSEMINATION: The Human Research Ethics Committee of the Queensland Children's Hospital approved the study. The trial results will be disseminated through conference presentations, teaching avenues and publications. TRIAL REGISTRATION NUMBER: ACTRN12619001686190; Pre-results.

Congenital airway lesions and lung disease.

Structural upper and lower airway disorders and parenchymal disorders are uncommon in pediatric practice, but many pediatricians will encounter them and be responsible for the ongoing care of these patients. Pediatricians need to be cognizant of these diagnoses because, even though management of these disorders generally lacks an evidence base, existing principles of good care surrounding accurate diagnosis, classifications of severity, judicious use of investigations, medication, and surgical approaches are essential to good outcomes.

Can CPAP Therapy in Pediatric OSA Ever Be Stopped?

STUDY OBJECTIVES: Continuous positive airway pressure (CPAP) has been increasingly used in children with obstructive sleep apnea (OSA), though it is unclear whether it can ever be ceased. We describe the clinical, demographic, and polysomnographic (PSG) characteristics of a cohort of children with OSA who were successfully weaned off CPAP. METHODS: From a pediatric cohort on CPAP for OSA at the Queensland Children's Hospital between January 2016 and December 2017, a subgroup of children who were taken off CPAP were retrospectively studied. RESULTS: CPAP therapy was stopped for 53 children over a 2-year period; 29 of these were excluded from analysis due to change to bilevel support (n = 2), transition to adult care (n = 12), or cessation due to poor adherence (n = 15). A total of 24 children [median (interquartile range, IQR) age 4.1 years (1.0-10.5); 18 males] were successfully weaned off CPAP therapy based on improvement in clinical and PSG parameters; and were included in the analysis. These children had a median (IQR) apnea-hypopnea index (AHI) of 9.8 (5.7-46.0) at CPAP initiation, which improved to 3.3 (0.4-2.2) at CPAP cessation after a median (IQR) duration of 1.0 (0.5-2.0) year. The reasons for CPAP cessation included improved symptoms and/or PSG parameters with time (n = 11); improvement after airway surgery (n = 7), and improvement of body mass index (n = 2). In four children, CPAP therapy was ceased after initial trial due to low physician perceived clinical benefit. CONCLUSIONS: This is the first study describing the characteristics of children and likely reasons for successful CPAP cessation. Children on CPAP should be regularly screened for ongoing CPAP need.

A comparison of virtual bronchoscopy versus flexible bronchoscopy in the diagnosis of tracheobronchomalacia in children.

INTRODUCTION: Flexible bronchoscopy (FB) is the current gold standard for diagnosing tracheobronchomalacia. However, it is not always feasible and virtual bronchoscopy (VB), acquired from chest multi-detector CT (MDCT) scan is an alternative diagnostic tool. We determined the sensitivity, specificity, and positive and negative predictive values of VB compared to FB in diagnosing tracheobronchomalacia. METHODS: Children aged <18-years scheduled for FB and MDCT were recruited. FB and MDCT were undertaken within 30-min to 7-days of each other. Tracheobronchomalacia (mild, moderate, severe, very severe) diagnosed on FB were independently scored by two pediatric pulmonologists; VB was independently scored by two pairs (each pair = pediatric pulmonologist and radiologist), in a blinded manner. RESULTS: In 53 children (median age = 2.5 years, range 0.8-14.3) evaluated for airway abnormalities, tracheomalacia was detected in 37 (70%) children at FB. Of these, VB detected tracheomalacia in 20 children, with a sensitivity of 54.1% (95%CI 37.1-70.2), specificity = 87.5% (95%CI 60.4-97.8), and positive predictive value = 90.9% (95%CI 69.4-98.4). The agreement between pediatric pulmonologists for diagnosing tracheomalacia by FB was excellent, weighted κ = 0.8 (95%CI 0.64-0.97); but only fair between the pairs of pediatric pulmonologists/radiologists for VB, weighted κ = 0.47 (95%CI 0.23-0.71). There were 42 cases of bronchomalacia detected on FB. VB had a sensitivity = 45.2% (95%CI 30.2-61.2), specificity = 95.5% (95%CI 94.2-96.5), and positive predictive value = 23.2 (95%CI 14.9-34.0) compared to FB in detecting bronchomalacia. CONCLUSION: VB cannot replace FB as the gold standard for detecting tracheobronchomalacia in children. However, VB could be considered as an alternative diagnostic modality in children with symptoms suggestive of tracheobronchomalacia where FB is unavailable. Pediatr Pulmonol. 2017;52:480-486. © 2016 Wiley Periodicals, Inc.

Cough quality in children: a comparison of subjective vs. bronchoscopic findings.

BACKGROUND: Cough is the most common symptom presenting to doctors. The quality of cough (productive or wet vs dry) is used clinically as well as in epidemiology and clinical research. There is however no data on the validity of cough quality descriptors. The study aims were to compare (1) cough quality (wet/dry and brassy/non-brassy) to bronchoscopic findings of secretions and tracheomalacia respectively and, (2) parent's vs clinician's evaluation of the cough quality (wet/dry). METHODS: Cough quality of children (without a known underlying respiratory disease) undergoing elective bronchoscopy was independently evaluated by clinicians and parents. A 'blinded' clinician scored the secretions seen at bronchoscopy on pre-determined criteria and graded (1 to 6). Kappa (K) statistics was used for agreement, and inter-rater and intra-rater agreement examined on digitally recorded cough. A receiver operating characteristic (ROC) curve was used to determine if cough quality related to amount of airway secretions present at bronchoscopy. RESULTS: Median age of the 106 children (62 boys, 44 girls) enrolled was 2.6 years (IQR 5.7). Parent's assessment of cough quality (wet/dry) agreed with clinicians' (K = 0.75, 95%CI 0.58-0.93). When compared to bronchoscopy (bronchoscopic secretion grade 4), clinicians' cough assessment had the highest sensitivity (0.75) and specificity (0.79) and were marginally better than parent(s). The area under the ROC curve was 0.85 (95%CI 0.77-0.92). Intra-observer (K = 1.0) and inter-clinician agreement for wet/dry cough (K = 0.88, 95%CI 0.82-0.94) was very good. Weighted K for inter-rater agreement for bronchoscopic secretion grades was 0.95 (95%CI 0.87-1). Sensitivity and specificity for brassy cough (for tracheomalacia) were 0.57 and 0.81 respectively. K for both intra and inter-observer clinician agreement for brassy cough was 0.79 (95%CI 0.73-0.86). CONCLUSIONS: Dry and wet cough in children, as determined by clinicians and parents has good clinical validity. Clinicians should however be cognisant that children with dry cough may have minimal to mild airway secretions. Brassy cough determined by respiratory physicians is highly specific for tracheomalacia.

High specificity of combined narrow band imaging and autofluorescence mucosal assessment of patients with head and neck cancer.

BACKGROUND: The purpose of this study was to evaluate combined autofluorescence (AF) and narrow band imaging (NBI) for detection of mucosal lesions additional to known primary head and neck cancers and to determine impact on management. METHODS: Patients with head and neck cancer requiring preoperative screening or posttreatment surveillance had white light (WL), AF and NBI inspection of the head and neck and bronchus. Known primary cancers were not analyzed, only additional lesions. Moderate dysplasia or worse was considered significant. RESULTS: In all, 73 patients were recruited. Respectively, there were 24 and 18 additional lesions in the head and neck and bronchus that had significant histopathology. In both regions, AF and NBI were more sensitive than WL for detecting significant dysplasia with NBI demonstrating better specificity than AF (p = .003); 11 of 73 patients (15.1%) had additional findings detected by AF and NBI, which had an impact on management. CONCLUSION: Combined AF and NBI inspection is highly specific at panendoscopy and can influence management.

A cough algorithm for chronic cough in children: a multicenter, randomized controlled study.

OBJECTIVES: The goals of this study were to: (1) determine if management according to a standardized clinical management pathway/algorithm (compared with usual treatment) improves clinical outcomes by 6 weeks; and (2) assess the reliability and validity of a standardized clinical management pathway for chronic cough in children. METHODS: A total of 272 children (mean ± SD age: 4.5 ± 3.7 years) were enrolled in a pragmatic, multicenter, randomized controlled trial in 5 Australian centers. Children were randomly allocated to 1 of 2 arms: (1) early review and use of cough algorithm ("early-arm"); or (2) usual care until review and use of cough algorithm ("delayed-arm"). The primary outcomes were proportion of children whose cough resolved and cough-specific quality of life scores at week 6. Secondary measures included cough duration postrandomization and the algorithm's reliability, validity, and feasibility. RESULTS: Cough resolution (at week 6) was significantly more likely in the early-arm group compared with the delayed-arm group (absolute risk reduction: 24.7% [95% confidence interval: 13-35]). The difference between cough-specific quality of life scores at week 6 compared with baseline was significantly better in the early-arm group (mean difference between groups: 0.6 [95% confidence interval: 0.29-1.0]). Duration of cough postrandomization was significantly shorter in the early-arm group than in the delayed-arm group (P = .001). The cough algorithm was reliable (κ = 1 in key steps). Feasibility was demonstrated by the algorithm's validity (93%-100%) and efficacy (99.6%). Eighty-five percent of children had etiologies easily diagnosed in primary care. CONCLUSIONS: Management of children with chronic cough, in accordance with a standardized algorithm, improves clinical outcomes irrespective of when it is implemented. Further testing of this standardized clinical algorithm in different settings is recommended.

Pulmonary function and long-term follow-up of children with tracheobronchomalacia.

BACKGROUND: Primary tracheobronchomalacia (TBM) is a disease of the large airways. Long-term follow-up studies of TBM patients have not been reported. This study was undertaken to further elicit the natural history of this condition and the presence of concomitant reactive airways disease through clinical profiling and pulmonary function testing. METHODS: Twenty-one children diagnosed with TBM by bronchoscopy between 1998 and 2001 in Queensland were recruited in 2008. Parents completed a questionnaire detailing their child's respiratory symptoms over the previous 12 months. Children then undertook pulmonary function and flow-volume loop classification. Mannitol bronchial provocation testing or post-bronchodilator spirometry was performed to assess for the confounding presence of reactive airways disease. RESULTS: Data from 19 children (12 males) were able to be analyzed. The median age was 9.4 (range 7.6-14.3) years. 15 parents indicated their child's symptoms were unresolved. The mean FEV(1) was 81% predicted with 7 <80% predicted. This was significantly lower than the percent predicted population mean (P = 0.0005). Mean FEV(1) /FVC, FEF(25-75) , and PEF were also significantly reduced (P = < 0.0001). Four participants had a classical TBM flow-volume loop on analysis. One of 15 (6.7%) participants recorded a positive test for reactive airways disease. CONCLUSIONS: Clinical symptom profiles and pulmonary function indicate persistent functional mechanical abnormalities of the large and small airways in TBM patients, and the absence of reactive airways disease.

Optical differentiation between malignant and benign lymphadenopathy by grey scale texture analysis of endobronchial ultrasound convex probe images.

BACKGROUND: Morphologic and sonographic features of endobronchial ultrasound (EBUS) convex probe images are helpful in predicting metastatic lymph nodes. Grey scale texture analysis is a well-established methodology that has been applied to ultrasound images in other fields of medicine. The aim of this study was to determine if this methodology could differentiate between benign and malignant lymphadenopathy of EBUS images. METHODS: Lymph nodes from digital images of EBUS procedures were manually mapped to obtain a region of interest and were analyzed in a prediction set. The regions of interest were analyzed for the following grey scale texture features in MATLAB (version 7.8.0.347 [R2009a]): mean pixel value, difference between maximal and minimal pixel value, SEM pixel value, entropy, correlation, energy, and homogeneity. Significant grey scale texture features were used to assess a validation set compared with fluoro-D-glucose (FDG)-PET-CT scan findings where available. RESULTS: Fifty-two malignant nodes and 48 benign nodes were in the prediction set. Malignant nodes had a greater difference in the maximal and minimal pixel values, SEM pixel value, entropy, and correlation, and a lower energy (P < .0001 for all values). Fifty-one lymph nodes were in the validation set; 44 of 51 (86.3%) were classified correctly. Eighteen of these lymph nodes also had FDG-PET-CT scan assessment, which correctly classified 14 of 18 nodes (77.8%), compared with grey scale texture analysis, which correctly classified 16 of 18 nodes (88.9%). CONCLUSIONS: Grey scale texture analysis of EBUS convex probe images can be used to differentiate malignant and benign lymphadenopathy. Preliminary results are comparable to FDG-PET-CT scan.

Longitudinal growth and lung function in pediatric non-cystic fibrosis bronchiectasis: what influences lung function stability?

BACKGROUND: Longitudinal FEV(1) data in children with non-cystic fibrosis (non-CF) bronchiectasis (BE) are contradictory, and there are no multifactor data on the evolution of lung function and growth in this group. We longitudinally reviewed lung function and growth in children with non-CF BE and explored biologically plausible factors associated with changes in these parameters over time. METHODS: Fifty-two children with > or = 3 years of lung function data were retrospectively reviewed. Changes in annual anthropometry and spirometry at year 3 and year 5 from baseline were analyzed. The impact of sex, age, cause, baseline FEV(1), exacerbation frequency, radiologic extent, socioeconomic status, environmental tobacco smoke exposure, and period of diagnosis was evaluated. RESULTS: Over 3 years, the group mean forced expiratory flow midexpiratory phase percent predicted and BMI z-score improved by 3.01 (P = .04; 95% CI, 0.14-5.86) and 0.089 (P = .01; 95% CI, 0.02-0.15) per annum, respectively. FEV(1)% predicted, FVC% predicted, and height z-score all showed nonsignificant improvement. Over 5 years, there was improvement in FVC% predicted (slope 1.74; P = .001) annually, but only minor improvement in other parameters. Children with immunodeficiency and those with low baseline FEV(1) had significantly lower BMI at diagnosis. Frequency of hospitalized exacerbation and low baseline FEV(1) were the only significant predictors of change in FEV(1) over 3 years. Decline in FEV(1)% predicted was large (but nonsignificant) for each additional year in age of diagnosis. CONCLUSIONS: Spirometric and anthropometric parameters in children with non-CF BE remain stable over a 3- to 5-year follow-up period once appropriate therapy is instituted. Severe exacerbations result in accelerated lung function decline. Increased medical cognizance of children with chronic moist cough is needed for early diagnosis, better management, and improving overall outcome in BE.

Combining autofluorescence and narrow band imaging with image analysis in the evaluation of preneoplastic lesions in the bronchus and larynx.

BACKGROUND AND OBJECTIVES: Autofluorescence (AF) techniques improve the diagnostic yield of white light inspection for preneoplastic lesions in the bronchus and head and neck region. Although highly sensitive, AF has poor specificity, particularly in situations where there have been earlier biopsies or treatments such as radiotherapy. Narrow band imaging (NBI) is a newer imaging technique that enhances the early abnormal angiogenesis seen in preneoplastic lesions. NBI has higher specificity when compared with AF. We aimed to combine these imaging modalities, using AF as an effective screening tool and NBI to confirm AF findings. We also used computer-assisted image analysis techniques to give objective confirmation to our visual inspection. METHODS: Three patients were selected for image analysis of their NBI images using the L*a*b* color scale in manually drawn regions of interest of biopsy-confirmed areas. Each case compared pathology with a different benign condition: normal tissue, postbiopsy effect, and postradiation therapy change. Patients had white light followed by AF inspection. Abnormal areas of AF were cross-examined with NBI. RESULTS: NBI clearly showed dysplasia and carcinoma in situ. It also confirmed abnormal fluorescence because of earlier biopsies and radiation therapy. Analysis of the L*a*b* color space scale in each case showed segmentation between pathology and the benign tissue. CONCLUSIONS: There may be additive and discriminatory benefits of NBI after AF inspection. Further study with computer-assisted color segmentation techniques and image analysis is required before optical diagnosis can become a reality in bronchoscopic techniques in the future.