Subclinical Tuberculosis in Children: Diagnostic Strategies for Identification Reported in a 6-year National Prospective Surveillance Study.

BACKGROUND: Subclinical tuberculosis (TB) is well recognized and defined as a disease state with absent or nonrecognized symptoms. The study identifies factors associated with subclinical TB and diagnostic strategies in a low-burden, high-resource country. METHODS: Data were collected between December 2013 and November 2019 through the Swiss Pediatric Surveillance Unit (SPSU). Children with culture/molecular confirmed TB, or who were treated with ≥3 antimycobacterial drugs, were included. RESULTS: A total of 138 (80%) children with TB disease were included in the final analysis, of which 43 (31%) were subclinical. The median age of children with subclinical compared to symptomatic TB was 3.7 (interquartile range [IQR] 2.2-7) and 9.7 (IQR 2.7-14.3) years, respectively (P = .003). The cause of investigation for TB was recorded in 31/43 (72.1%) of children with subclinical TB and included contact exposure in 25 (80.6%) of children. In children with subclinical TB, diagnosis was made by a combination of the following abnormal/confirming results: culture/molecular + immunodiagnostic + chest radiography in 12 (27.9%) cases, immunodiagnostic + chest radiography in 19 (44.2%) cases, culture/molecular + chest radiography in 2 (4.7%) cases, culture + immunodiagnostic in 1 (2.3%) case, chest radiography only in 8 (18.6%) cases, and immunodiagnostic only in 1 (2.3%) case. CONCLUSIONS: A notable proportion of children with TB had subclinical disease. This highlights the importance of non-symptom-based TB case finding in exposed children and refugees from high-TB-prevalence settings. TB screening in these asymptomatic children should therefore include a combination of immunodiagnostic testing and imaging followed by culture and molecular testing.

Pediatric Tuberculosis Disease during Years of High Refugee Arrivals: A 6-Year National Prospective Surveillance Study.

BACKGROUND: In Europe, surveillance and monitoring of pediatric tuberculosis (TB) remains important, particularly in the light of migration in recent years. The aim of the study was to evaluate incidence rates of childhood TB and detailed diagnostic pathways and treatment. METHODS: Data were collected through the Swiss Pediatric Surveillance Unit (SPSU) from December 2013 to November 2019. Monthly -notifications are obtained from the 33 pediatric hospitals in the SPSU, and a detailed questionnaire was sent out upon notification. Inclusion criteria were children and adolescents aged up to 15 years with culture- or molecular-confirmed TB disease or for whom a treatment with ≥3 antimycobacterial drugs had been initiated. Data were compared with age-matched notification data from the Swiss Federal Office of Public Health (FOPH). RESULTS: Of the 172 cases notified to SPSU, a detailed questionnaire was returned for 161 (93%) children, of which 139 met the inclusion criteria. Reasons for exclusion were age >15 years, double reporting, and not fulfilling the criteria for TB disease. During the same time period, 172 pediatric TB cases were reported to the FOPH, resulting in an incidence of 2.1 per 100,000, ranging from 1.4 to 2.8 per year, without a clear trend over time. In the 64 (46.0%) foreign-born children, incidence rates were higher and peaked in 2016, with 13.7 per 100,000 (p = 0.018). The median interval between arrival in Switzerland and TB diagnosis was 5 (IQR 1-21) months, and 80% were diagnosed within 24 months of arrival. In 58% of the cases, TB disease was confirmed by culture or molecular assays. Age >10 years, presence of fever, or weight loss were independent factors associated with confirmed TB. CONCLUSION: The annual pediatric TB incidence rate only varied among foreign-born children and was highest in 2016 when refugee influx peaked in Europe. Importantly, most foreign-born children with TB were diagnosed within 2 years after arrival in Switzerland. Thus, the early period after arrival in Switzerland is associated with a higher risk of TB disease in children, and this should be considered for screening guidance in refugees.

Pediatric Airway Endoscopy: Recommendations of the Society for Pediatric Pneumology.

For many decades, pediatric bronchoscopy has been an integral part of the diagnosis and treatment of acute and chronic pulmonary diseases in children. Rapid technical advances have continuously influenced the performance of the procedure. Over the years, the application of pediatric bronchoscopy has considerably expanded to a broad range of indications. In this comprehensive and up-to-date guideline, the Special Interest Group of the Society for Pediatric Pneumology reviewed the most recent literature on pediatric bronchoscopy and reached a consensus on a safe technical performance of the procedure.

CPAP to diagnose laryngeal clefts by flexible endoscopy in infants.

BACKGROUND: Laryngeal clefts (LC) are uncommon but important causes of stridor in infants. Direct laryngoscopy is the recommended method for the detection of LC because LC may be missed by flexible endoscopy. As laryngomalacia by far outnumbers any other cause of stridor in this age group flexible bronchoscopy is usually the preferred method for the evaluation of significant infantile stridor. The aim is to illustrate how the application of CPAP assists the detection of LC during flexible endoscopy. METHOD: Continuous positive airway pressure (CPAP) is applied via endoscopy mask during flexible endoscopy, titrated to open the upper esophageal sphincter, and to spread the inter-arytenoid folds. RESULTS: The application of CPAP of 10-15 cmH2 O resulted in visual unmasking of otherwise obscured LC in four young children assessed for congenital stridor. CONCLUSION: CPAP helps visualize LC by flexible endoscopy obviating transition to direct laryngoscopy and manual exploration.

Topical Lidocaine Does Not Exaggerate Laryngomalacia in Infants During Flexible Bronchoscopy Under Propofol Anesthesia.

BACKGROUND: Topical lidocaine has been found to result in overestimation of the severity of laryngomalacia in infants undergoing flexible bronchoscopy under conscious sedation with midazolam and nalbuphine. This effect has never been confirmed and may depend on the level of sedation and the drugs used. We assessed the effect of topical lidocaine on laryngomalacia in infants undergoing flexible bronchoscopy under general anesthesia with propofol. METHODS: Thirteen infants with congenital stridor referred to diagnostic flexible video-bronchoscopy were studied under propofol anesthesia before and 3 minutes after topical lidocaine administration to the larynx at a dose of 3 mg/kg body weight. Laryngomalacia was scored using 60 seconds video recordings of the larynx before and after lidocaine administration in random order by 2 independent blinded observers using the previously described arytenoid score (AS), epiglottis score (ES), and the total score (TS=AS+ES). RESULTS: No significant differences in AS, ES, and laryngomalacia score were found between the prelidocaine and postlidocaine assessments by the 2 raters. The intraclass correlation coefficients were 0.995 (95% confidence interval, 0.986-0.998) and 0.975 (0.930-0.991) and 0.989 (0.971-996) for AS, ES, and TS, respectively. CONCLUSIONS: The assessment of laryngomalacia is not affected by topical lidocaine under propofol anesthesia. The lidocaine effect on laryngomalacia may vary depending on the medication regime used and the depth of procedural sedation.

Effect of a smoking ban on respiratory health in nonsmoking hospitality workers: a prospective cohort study.

OBJECTIVE: The aim of this study was to examine the effect of a smoking ban on lung function, fractional exhaled nitric oxide, and respiratory symptoms in nonsmoking hospitality workers. METHODS: Secondhand smoke exposure at the workplace, spirometry, and fractional exhaled nitric oxide were measured in 92 nonsmoking hospitality workers before as well as twice after a smoking ban. RESULTS: At baseline, secondhand smoke-exposed hospitality workers had lung function values significantly below the population average. After the smoking ban, the covariate-adjusted odds ratio for cough was 0.59 (95% confidence interval, 0.36 to 0.93) and for chronic bronchitis 0.75 (95% confidence interval, 0.55 to 1.02) compared with the preban period. CONCLUSIONS: The below-average lung function before the smoking ban indicates chronic damages from long-term exposure. Respiratory symptoms such as cough decreased within 12 months after the ban.

The prevalence of tracheal bronchus in pediatric patients undergoing rigid bronchoscopy.

BACKGROUND: Tracheal bronchus (TB) is defined as an abnormal bronchus that originates directly from the lateral wall of the trachea above the carina and goes towards the upper lobe territory of the lung. We analyzed rigid endoscopies of the trachea in children to determine the incidence and characteristics of TB. METHODS: In total, 1021 rigid endoscopies of the trachea recorded from children aged 0 to 6 years were analyzed. Endoscopic examination was performed from supraglottic region to carina using a 0-degree Hopkins rod-lens telescope. Patients with a TB were identified and the site of origin of the TB and its level above the carina was noted. Data of the identified patients was reviewed for the presence of preoperative airway findings such as stridor, upper lobe pneumonia and wheezing or atelectasis, other congenital anomalies, and intraoperative complications. RESULTS: TB was detected in 11 (1.06%) of 1021 upper airway endoscopic examinations. All originated from the right lateral wall of the trachea. Six children had retained secretions in the TB, and 3 children had perioperative airway problems unrelated to the TB. One child showed right main stem bronchus narrowing as seen at the true carina, in the presence of a TB. All the children with TB exhibited at least 1 additional congenital anomaly at birth besides TB. CONCLUSIONS: TB is a relatively common congenital endoscopic lower airway anomaly in childhood, which is itself rarely symptomatic, but almost always coexists with other congenital anomalies.

Endoscopic airway findings in children with or without prior endotracheal intubation.

BACKGROUND: Airway alterations found after endotracheal intubation are usually associated with mechanical trauma from the tube. However, no studies are available concerning alterations in airways that have never been intubated before. It was the aim of the study to compare endoscopic findings in the larynx and trachea of children who had undergone prior endotracheal intubation with findings in children who had not been intubated before. METHODS: In 1021 children aged from 0 to 6 years, rigid endoscopies were performed before planned elective endotracheal intubation. The anonymized endoscopy videos were reviewed and graded by five international airway experts. Data was compared between the two groups using the chi-square test (P ≤ 0.05). RESULTS: Endoscopic records of 971 children (473 with prior intubation; 498 without prior airway intubation) were included in the final calculations. Most patients (93.7%) with prior intubation had been intubated with a cuffed tube. The number of intubations ranged from 1 to 27. The median interval between intubation and endoscopy was 0.53 years (0.003-5.57 years). Abnormal findings were observed in 31.7% and 26.8% of patients with and without prior intubation, respectively (P = 0.063). Glottic granulomas were significantly more common after intubation (3.6% vs 1.4%; P = 0.028). The incidence of other abnormal findings was similar in both groups. CONCLUSION: Endoscopic airway alterations can be observed in about one-quarter of children presenting for routine surgery without prior intubation. Except for glottic granulomas, the abnormalities are found with similar frequency in patients with and without prior intubation. No relevant airway damage from short-term endotracheal intubation was found.

Progressive static pulmonary hyperinflation in survivors of severe bronchopulmonary dysplasia by mid-adulthood.

BACKGROUND: Severe bronchopulmonary dysplasia (BPD) might be associated with an accelerated age-related decline of lung function. METHODS: 14 individuals were studied longitudinally at 15±4, 18±3 and 38±3.2 years. Information on personal history was completed, and lung function testing and skin prick testing were performed. Longitudinal data were compared intra-individually and with matched controls from the NHANES III dataset. RESULTS: The ratio of residual volume/total lung capacity (RV/TLC) increased markedly from 25.9±7.0% to 39.3±6.8%. A significant time-effect was found compared to controls for the forced vital capacity (FVC) which decreased more rapidly than expected. Flow values were at the lower limit of normal range but remained relatively stable over time. Some individuals had completely normal lung function results. CONCLUSION: Increasing static pulmonary hyperinflation with age is indicative of bronchiolar dysfunction or early emphysematous changes in survivors of severe BPD. Susceptibility for long-term sequelae shows significant variability.

Nanoduct sweat testing for rapid diagnosis in newborns, infants and children with cystic fibrosis.

Determination of chloride concentration in sweat is the current diagnostic gold standard for Cystic Fibrosis (CF). Nanoduct is a new analyzing system measuring conductivity which requires only 3 microliters of sweat and gives results within 30 minutes. The aim of the study was to evaluate the applicability of this system in a clinical setting of three children's hospitals and borderline results were compared with sweat chloride concentration. Over 3 years, 1,041 subjects were tested and in 946 diagnostic results were obtained. In 95 children, Nanoduct failed (9.1% failure rate), mainly due to failures in preterm babies and newborns. Assuming 59 mmol/L as an upper limit of normal conductivity, all our 46 CF patients were correctly diagnosed (sensitivity 100%, 95% CI: 93.1-100; negative predicted value 100% (95% CI: 99.6-100) and only 39 non CF's were false positive (39/900, 4.3%; specificity 95.7%, 95%CI: 94.2-96.9, positive predicted value 54.1% with a 95%CI: 43.4-65.0). Increasing the diagnostic limit to 80 mmol/L, the rate fell to 0.3% (3/900). CF patients had a median conductivity of 115 mmol/L; the non-CF a median of 37 mmol/L. In conclusion, the Nanoduct test is a reliable diagnostic tool for CF diagnosis: It has a failure rate comparable to other sweat tests and can be used as a simple bedside test for fast and reliable exclusion, diagnosis or suspicion of CF. In cases with borderline conductivity (60-80 mmol/L) other additional methods (determination of chloride and genotyping) are indicated.

Decrease in functional residual capacity and ventilation homogeneity after neuromuscular blockade in anesthetized preschool children in the lateral position.

BACKGROUND: While functional residual capacity (FRC) is reduced in children undergoing general anesthesia, the lateral position leads to an increase in FRC compared with the supine position. The impact of neuromuscular blockade remains unknown. We tested the hypothesis that neuromuscular blockade leads to a decrease in FRC and increase in lung clearance index (LCI) while the application of positive endexpiratory pressure (PEEP) of 6 cmH(2)O leads to a restoration in both parameters. METHODS: After approval of the local Ethics Committee, we studied 18 preschool children (2-6 years) without cardiopulmonary disease, who were scheduled for elective surgery. Anesthesia was standardized using propofol and fentanyl. FRC and LCI were calculated by a blinded observer using a SF6 multibreath washout technique with an ultrasonic transit-time airflow meter (Exhalyzer D). Measurements were taken in the left lateral position (PEEP 3 cmH2O) after 1. intubation with a cuffed tracheal tube, 2. neuromuscular blockade with rocuronium, and 3. the additional application of PEEP (6 cmH2O). RESULTS: Functional residual capacity mean (sd) decreased from 31.6 (4.4) ml.kg(-1) to 27.6 (4.2) ml.kg(-1) (P<0.001) following neuromuscular blockade while the LCI increased from 6.54 (0.6) to 7.0 (0.6) (P

Ultrastructural and molecular analysis in fatal neonatal interstitial pneumonia caused by a novel ABCA3 mutation.

Pulmonary surfactant is essential to maintain alveolar patency, and invariably fatal neonatal lung disease has been recognized to involve mutations in the genes encoding surfactant protein-B or ATP-binding cassette transporter family member ABCA3. The lipid transporter ABCA3 targets surfactant phospholipids to lamellar bodies that are lysosomal-derived organelles of alveolar type II cells. ABCA3-/- mice have grossly reduced surfactant phosphatidyl glycerol levels and die of respiratory failure soon after birth. We studied lung biopsy samples of two siblings with a novel homozygous ABCA3 mutation at nucleotide position 578 (c.578C>G), leading to a Pro193Arg amino-acid exchange, who died at 55 and 105 days of age. Light microscopy revealed thickened alveolar septa with abundant myxoid interstitial matrix, marked hyperplasia of type II pneumocytes, desquamation of alveolar macrophages and focal alveolar proteinosis. Surfactant protein-B was detected by immunohistochemistry after antigen retrieval. Transmission electron microscopy showed rare cytoplasmic inclusions with concentric membranes and eccentrically placed electron-dense aggregates. These 'fried-egg'-appearing lamellar bodies differed both from normal lamellar bodies and the larger, poorly formed composite bodies with multiple vesicular inclusions observed in surfactant protein-B deficiency. In conclusion, our findings underscore that the implications of interstitial lung disease in infant lungs differ from those in adults. In infants with a desquamative interstitial pneumonitis pattern, surfactant or ABCA3 mutations should be evaluated. Importantly, these findings support the notion that electron microscopy is useful in distinguishing between surfactant protein-B and ABCA3 deficiency, and has an important role in evaluating biopsies or autopsies of term infants with unexplained severe respiratory failure and interstitial lung disease.

Prone equals prone? Impact of positioning techniques on respiratory function in anesthetized and paralyzed healthy children.

OBJECTIVES: Although the prone position is effectively used to improve oxygenation, its impact on functional residual capacity is controversial. Different techniques of body positioning might be an important confounding factor. The aim of this study was to determine the impact of two different prone positioning techniques on functional residual capacity and ventilation distribution in anesthetized, preschool-aged children. DESIGN: Functional residual capacity and lung clearance index, a measure of ventilation homogeneity, were calculated using a sulfur-hexafluoride multibreath washout technique. After intubation, measurements were taken in the supine position and, in random order, in the flat prone position and the augmented prone position (gel pads supporting the pelvis and the upper thorax). SETTING: Pediatric anesthesia unit of university hospital. PATIENTS AND PARTICIPANTS: Thirty preschool children without cardiopulmonary disease undergoing elective surgery. MEASUREMENTS AND RESULTS: Mean (range) age was 48.5 (24-80) months, weight 17.2 (10.5-26.9) kg, functional residual capacity (mean +/- SD) 22.9+/- 6.2 ml.kg (-1) in the supine position and 23.3 +/- 5.6 ml.kg (-1) in the flat prone position, while lung clearance indices were 8.1 +/- 2.3 vs. 7.9 +/- 2.3, respectively. In contrast, functional residual capacity increased to 27.6 +/- 6.5 ml.kg (-1) (p< 0.001) in the augmented prone position while at the same time the lung clearance index decreased to 6.7 +/- 0.9 (p< 0.001). CONCLUSIONS: Functional residual capacity and ventilation distribution were similar in the supine and flat prone positions, while these parameters improved significantly in the augmented prone position, suggesting that the technique of prone positioning has major implications for pulmonary function.

Nasal nitric oxide measurements to screen children for primary ciliary dyskinesia.

STUDY OBJECTIVE: To examine the usefulness of exhaled and nasal nitric oxide (NO) measurements to detect primary ciliary dyskinesia (PCD) in children. DESIGN AND METHODS: The study population consisted of 34 children with symptoms suggestive of PCD who were previously referred to our pediatric university respiratory disease clinic for a diagnostic workup including analysis of ciliary structure and function by respiratory mucosal biopsy. PCD was diagnosed in 17 of the 34 children according to the ciliary biopsy results. Measurements of nasal and exhaled NO were performed according to European Respiratory Society and American Thoracic Society guidelines in the patients with and without biopsy-proven PCD, and also in 24 healthy age-matched subjects. RESULTS: Nasal NO was significantly lower in those children with proven PCD (geometric mean; 13.7 parts per billion [ppb]), compared to those who had negative biopsy results (132.7 ppb) and healthy control subjects (223.7 ppb). The measurement of nasal NO in our study population showed, below a cut-off level of < 105 ppb, a specificity of 88% for PCD, and positive predictive value of 89%. Nasal NO above a cut-off level of 105 ppb excluded PCD with a 100% certainty. The lower levels of exhaled NO in patients with PCD did not reach statistical significance. CONCLUSION: The measurement of nasal NO appears to be a useful tool to screen children for PCD and to exclude this disease in those with high nasal NO levels.

Acquired upper airway obstruction.

Acquired upper airway obstruction is a common cause of respiratory emergencies in children. Most pathologic processes that result in upper airway compromise are a consequence of infection, trauma or aspiration. Today, many of the infectious causes of upper airway obstruction have lost their threat as a result of the progress made in preventing and treating these infections. Prompt recognition and appropriate management of the child presenting with upper airway obstruction remains critical, because certain causes can progress rapidly from a mild to a potentially life-threatening disease state. A correct diagnosis can often be made by history and physical examination, but additional studies may be useful in selected cases. The child's clinical appearance is the most reliable indicator of severity, and measurable signs are of less value. If respiratory failure is imminent, airway protection and endoscopy for definitive diagnosis may have priority over any other therapeutic or diagnostic procedure.

Inhaled nitric oxide therapy in neonates and children: reaching a European consensus.

Inhaled nitric oxide (iNO) was first used in neonatal practice in 1992 and has subsequently been used extensively in the management of neonates and children with cardiorespiratory failure. This paper assesses evidence for the use of iNO in this population as presented to a consensus meeting jointly organised by the European Society of Paediatric and Neonatal Intensive Care, the European Society of Paediatric Research and the European Society of Neonatology. Consensus Guidelines on the Use of iNO in Neonates and Children were produced following discussion of the evidence at the consensus meeting.

Effect of forced deflation maneuvers upon measurements of respiratory mechanics in ventilated infants.

OBJECTIVE: To determine the effect of forced deflation maneuvers on respiratory mechanics and to assess the reproducibility of such measurements in intubated infants with lung disease. DESIGN AND SETTING: Prospective study in the pediatric intensive care unit of a university children's hospital. PATIENTS: Ten clinically stable infants requiring mechanically assisted ventilation for acute pulmonary disease, mean age 5.9 months (1-18), mean weight 5.8 kg (3.2-13). INTERVENTIONS: Two sets of measurements of compliance (Crs) and resistance (Rrs) were obtained at 20-min intervals both before and after +40/-40 cmH(2)O forced deflation maneuvers. Forced deflation measurements were repeated at the end of the study. RESULTS: . Forced deflation caused a significant increase in Crs from 0.53+/-0.09 and 0.58+/-0.11 ml/cmH(2)O/kg to 0.71+/-0.11 and 0.68+/-0.11 ml/cmH(2)O/kg. Rrs measurements did not differ. The low coefficients of variation for repeated measures of the baseline measurements (Crs 4.2+/-0.5%, Rrs 7.1+/-0.8%, for forced vital capacity 8.6+/-2.5%, maximum expiratory flows at 25% vital capacity 16.0%+/-3.3%) confirmed the good reproducibility during stable conditions. CONCLUSIONS: Inflation and deflation maneuvers affect subsequent measurements of respiratory system compliance but not measurements of maximum expiratory flow-volume relationships in intubated infants, probably through recruitment of lung volume. Careful interpretation and planning of the sequence of infant pulmonary function testing is necessary to reassure that changes are not related to short-term alterations in volume history.