Validation of computerized wheeze detection in young infants during the first months of life.

BACKGROUND: Several respiratory diseases are associated with specific respiratory sounds. In contrast to auscultation, computerized lung sound analysis is objective and can be performed continuously over an extended period. Moreover, audio recordings can be stored. Computerized lung sounds have rarely been assessed in neonates during the first year of life. This study was designed to determine and validate optimal cut-off values for computerized wheeze detection, based on the assessment by trained clinicians of stored records of lung sounds, in infants aged <1 year. METHODS: Lung sounds in 120 sleeping infants, of median (interquartile range) postmenstrual age of 51 (44.5-67.5) weeks, were recorded on 144 test occasions by an automatic wheeze detection device (PulmoTrack®). The records were retrospectively evaluated by three trained clinicians blinded to the results. Optimal cut-off values for the automatically determined relative durations of inspiratory and expiratory wheezing were determined by receiver operating curve analysis, and sensitivity and specificity were calculated. RESULTS: The optimal cut-off values for the automatically detected durations of inspiratory and expiratory wheezing were 2% and 3%, respectively. These cutoffs had a sensitivity and specificity of 85.7% and 80.7%, respectively, for inspiratory wheezing and 84.6% and 82.5%, respectively, for expiratory wheezing. Inter-observer reliability among the experts was moderate, with a Fleiss' Kappa (95% confidence interval) of 0.59 (0.57-0.62) for inspiratory and 0.54 (0.52 - 0.57) for expiratory wheezing. CONCLUSION: Computerized wheeze detection is feasible during the first year of life. This method is more objective and can be more readily standardized than subjective auscultation, providing quantitative and noninvasive information about the extent of wheezing.

Metals in female scalp hair globally and its impact on perceived hair health.

Globally, billions of individuals wash their hair in water, which acts as an exogenous metal source. Many studies which measure the metal levels found on human hair specifically aim to remove exogenous materials prior to analysis. Although this is needed when using hair analysis to probe the impact of the local environment on endogenous metal levels, it is not relevant for understanding exactly what is on hair as a result of contact with its daily environment. Understanding these levels are important, as the presence of redox active metals, such as copper and iron, can impact fibre health, either as a result of UV irradiation, or during the hair colouring process. A global hair sampling study of over 300 individuals from nine countries has been performed, and the combined endogenous and exogenous metals analysed. The levels measured vary widely, even within the narrow geography of each hair sampling location. The levels of calcium, magnesium, copper and iron were not correlated, and within each location, there are expected to be individuals with high metal levels. Levels increased from hair root to tip for calcium, magnesium and copper, attributed to hair contact with the environment showing the impact of exogenous metals in the overall levels on hair. Levels of redox metals were comparable between individuals who coloured or did not colour their hair, although water hardness ions were statistically significantly higher for hair colouring individuals. Individuals who perceived their hair health as poor had higher metal levels on their hair. Controlling metals on hair, either by preventing their binding during environmental contact, or through controlling their ability to cause hair damage, should lead to improved consumer perceived hair health.

Children with nocturnal asthma wheeze intermittently during sleep.

Nocturnal asthma indicates poor overall control of asthma and adversely affects the quality of life of the patient. The purpose of the present study was to compare the objective measurement of nocturnal wheeze with clinical state, recall of symptoms, and changes in lung function. Nine asthmatic children aged 9 to 16 years were followed with an asthma diary and diurnal measurement of peak flow for a week before the nocturnal study; all but two were apparently well controlled. Breath sounds were recorded and analyzed continuously overnight to quantify wheeze using a phonopneumography sensor attached over the trachea. The analytical system (PulmoTrack) utilized an algorithm to detect wheeze and reject interference. The wheeze rate (Tw/Ttot = duration of wheeze/duration of recording) was calculated minute by minute throughout the night. Recordings lasted over 8 hours and all but two children had wheeze lasting for a total time of between 11 and 87 minutes. The pattern of wheezing was very variable during sleep, with episodes of wheeze separated by periods of quiet breathing. There was no relationship between subjective perception of nocturnal asthma, forced expiratory volume in 1 s (FEV(1)) next morning, and the objective measurement of wheeze. Total overnight wheeze was significantly related to the total diary symptom score and to the (small) diurnal variability of peak expiratory flow (PEF). Four of the seven children with asthma who were apparently well controlled had considerable amounts of wheeze during the night that was episodic in nature and unrelated to conventional measures of lung function or nocturnal symptoms.

Suspected foreign body inhalation in children: what are the indications for bronchoscopy?

OBJECTIVE: To define the criteria for bronchoscopy in children with suspected foreign body (FB) inhalation. STUDY DESIGN: Health history, physical examination, and radiologic examination were performed before bronchoscopy in all children referred for suspected FB inhalation between 2003 and 2005. RESULTS: A total of 142 children, ranging in age from 3 months to 14 years (median age, 20 months), were referred with a history of suspected FB inhalation. An FB was found in 42 children with abnormal physical and radiologic findings, in 17 children with abnormal physical or radiologic findings, and in 2 children with normal physical and radiologic finding but persistent cough. Bronchoscopy revealed no FB in the children with normal physical and radiologic examinations and no symptoms (n = 16). CONCLUSION: In children with a history of choking, bronchoscopy is mandatory in the presence of persistent symptoms, such as cough, dyspnea, and fever, or any abnormal physical or chest radiography findings. Bronchoscopy is not necessary in asymptomatic children with normal physical and radiographic examinations.

The use of bronchial challenge to diagnose asthma in preschool children.

Wheezing and respiratory symptoms are very common in preschool children, and the ability to diagnose asthma correctly is important. This review describes an approach to the diagnosis of asthma in preschool children by means of an inhalation bronchial challenge. The child is exposed to increasing doses of challenge agent until wheezing is detected at a dose below that at which normal subjects respond, thus indicating bronchial hyperreactivity. The technique was originally developed using simple stethoscope auscultation of the lungs together with recording of respiratory rate and oxygen saturation (by pulse oximetry). Extensive studies have confirmed the safety and practicability of the technique and the specificity for asthma when the challenge agent is adenosine 5'-monophosphate (AMP). Subsequently, acoustic recordings have been used to detect and analyse breath sounds and to quantify the wheeze; these show excellent correlation between the clinical detection of wheeze and the wheeze rate (duration of wheeze/duration of recording) during bronchial challenges in children. Equipment is now becoming available that can perform the acoustic quantification of wheeze automatically and facilitate bronchial challenges in young children.

Aqueous MEA and Ammonia Sorption-Induced Damage in Keratin Fibers.

The sorption of aqueous monoethanolamine (MEA) and ammonia solutions in keratin fibers and its subsequent effect on their mechanical performance has been investigated. The diffusion kinetics of MEA into keratin fibers for 0.1, 1.0, and 5 v/v % MEA in water at 30 and 50 °C were found to exhibit two clear regimes of absorption behavior: a linear Fickian diffusion regime for initial times up to 100 min, after which a second slower uptake process was observed. Single fiber tensile tests showed that the Young's modulus and the tensile failure stress for 5% MEA-treated fibers, compared to untreated fibers, were 25% lower after 1 h of treatment and 50% lower after 9 h of treatment. Aqueous treatments of 0.1 and 1% MEA, as well as 0.6 and 3% aqueous ammonia, had no measurable effect on either Young's modulus or tensile failure stress for the fibers. Scanning electron microscopy images and protein content analysis confirmed that keratin fibers exposed to 5% MEA solution exhibited significant surface damage as well as high levels of protein loss. This study confirms for the first time the important damage hair treatments containing 5% aqueous MEA can cause on keratin fibers.

Non-invasive forced expiratory flow-volume curves to measure lung function in cats.

Forced expiratory flow-volume curves were performed in 15 cats using the non-invasive thoracic compression techniques developed for use in human infants. Cats breathed through a face mask and pneumotachygraph from which flow and volume were obtained. Thoracic compression was applied from an inflatable bag in a non-expandable jacket surrounding the animal. Bag inflation at end inspiration was initiated by a computer pulse to a pressurized chamber. Processed signals from the pneumotachygraph determined maximum-forced expiratory flow at lung volume equivalent to functional residual capacity (FRC), termed V'maxFRC. Different compression pressures were used, and the highest value from a technically satisfactory flow-volume loop was taken as the result. Mean (+/- 95% CI) V'maxFRC was 422 (369-475) ml/s. Compared with infants of similar weight (V'maxFRC approximately 180 ml/s), cats had a much higher V'maxFRC. Tests repeated another day showed a mean (+/-95% CI) percentage difference between paired tests to be 2.8 (-12.6, +18.3)%. Non-invasive forced expiratory flow-volume measurements can be reliably obtained in sedated cats.

Non-invasive measurement of total respiratory compliance and resistance in cats.

We adapted non-invasive techniques developed for human infants to measure total respiratory system compliance (Crs) and resistance (Rrs) in 21 healthy cats. The animals breathed through a face mask attached to a respiratory circuit and measurements were taken of changes in lung volume and airway pressure during brief occlusions of the airway at different lung volumes. The slope of the plot of change in volume against airway pressure yielded the multiple occlusion Crs with a mean (+/-95%CI) value of 6.8 (6.3-7.3) ml/cm H2O. In 12 animals measurements were made by the single breath technique in which occlusion was made early in expiration and on release, a plot of the subsequent relaxed expiratory flow and volume yielded the time constant (taurs), Crs and Rrs with mean (+/-95%CI) values of 0.27 (0.22-0.31) s, 7.0 (6.1-7.8) ml/cm H2O, and 38.7 (33.7-43.6) cm H2O/l/s, respectively. Rrs was significantly correlated inversely with forced expiratory flow at resting lung volume (V'maxFRC).

Computerized acoustic assessment of treatment efficacy of nebulized epinephrine and albuterol in RSV bronchiolitis.

AIM: We evaluated the use of computerized quantification of wheezing and crackles compared to a clinical score in assessing the effect of inhaled albuterol or inhaled epinephrine in infants with RSV bronchiolitis. METHODS: Computerized lung sounds analysis with quantification of wheezing and crackles and a clinical score were used during a double blind, randomized, controlled nebulized treatment pilot study. Infants were randomized to receive a single dose of 1 mgr nebulized l-epinephrine or 2.5 mgr nebulized albuterol. Computerized quantification of wheezing and crackles (PulmoTrack) and a clinical score were performed prior to, 10 minutes post and 30 minutes post treatment. Results were analyzed with Student's t-test for independent samples, Mann-Whitney U test and Wilcoxon test. RESULTS: 15 children received albuterol, 12 received epinephrine. The groups were identical at baseline. Satisfactory lung sounds recording and analysis was achieved in all subjects. There was no significant change in objective quantification of wheezes and crackles or in the total clinical scores either within the groups or between the groups. There was also no difference in oxygen saturation and respiratory distress. CONCLUSION: Computerized lung sound analysis is feasible in young infants with RSV bronchiolitis and provides a non-invasive, quantitative measure of wheezing and crackles in these infants.

Relationship between computerized wheeze detection and lung function parameters in young infants.

OBJECTIVE: Computerized respiratory sound analysis (CORSA) has been validated in the assessment of wheeze in infants, but it is unknown whether automatically detected wheeze is associated with impaired lung function. This study investigated the relationship between wheeze detection and conventional lung function testing (LFT) parameters. METHODS: CORSA was performed using the PulmoTrack® monitor in 110 infants, of median (interquartile range) postmenstrual age 50 (46-56) weeks and median body weight 4,810 (3,980-5,900) g, recovering from neonatal intensive care. In the same session, LFT was performed, including tidal breathing measurements, occlusion tests, body plethysmography, forced expiratory flow by rapid thoracoabdominal compression, sulfur hexafluoride (SF6 ) multiple breath washout (MBW), and capillary blood gas analysis. Infants were classified as wheezers or non-wheezers using predefined cut-off values for the duration of inspiratory and expiratory wheeze. RESULTS: Wheezing was detected in 72 (65%) infants, with 43 (39%) having inspiratory and 53 (48%) having expiratory wheezing. Endotracheal mechanical ventilation in the neonatal period for > 24 hr was associated with inspiratory wheeze (P = 0.009). Airway resistance was increased in both inspiratory (P = 0.02) and expiratory (P = 0.004) wheezers and correlated with the duration of expiratory wheeze (r = 0.394, P < 0.001). Expiratory wheezers showed a significant increase in respiratory resistance (P = 0.001), time constant (0.012), and functional residual capacity using SF6 MBW (P = 0.019). There was no association between wheezing and forced expiratory flow or blood gases. CONCLUSION: CORSA can help identify neonates and young infants with subclinical airway obstruction and may prove useful in the follow-up of high-risk infants.

Timing and nature of wheezing at the endpoint of a bronchial challenge in preschool children.

Bronchial reactivity to inhaled agents in preschool children can be undertaken by auscultating the lungs to detect wheezing, but there is a lack of information on when wheeze first appears at the endpoint of the challenge and on the acoustic characteristics of the wheeze. We recorded breath sounds continuously during tidal breathing inhalation challenges with adenosine 5'-monophosphate, using sensors attached over each upper lobe in 80 preschool children. In 35 children, the challenge was considered positive by a pediatrician who determined the endpoint by detecting wheeze on auscultation after an inhalation. Using acoustic analysis, we determined that the first wheeze appeared during the 2-min period of nebulization in 31% of positive challenges; it was unilateral in 37%, and only inspiratory in 46%. A running window of 6 sec was used to detect at least two wheezes without reference to phase of breathing, and this index had a sensitivity of 97.6% and specificity of 99.7% for determining the endpoint of a challenge. Detecting wheeze acoustically adds safety to the technique by enabling the challenge to be stopped earlier, while the lack of a need to document the phase of breathing simplifies the technique.

Relapsing polychondritis: reversible airway obstruction is not always asthma.

Relapsing polychondritis (RP) is a rare disease characterized by recurrent inflammation of cartilaginous and other proteoglycan-rich tissues. Respiratory tract involvement is a common cause of morbidity and mortality in RP. We describe a patient whose clinical features at onset of disease were typical of asthma. Later, the patient developed symptoms and signs characteristic of RP. Tracheobronchomalacia necessitated airway support by stenting. The possibility that airway obstruction in the initial stages of RP is due to airway inflammation and that early, aggressive immunosuppressive treatment of RP may delay or prevent irreversible cartilaginous destruction and airway collapse are discussed.

Pulmonary hemorrhage/hemoptysis in children.

Pulmonary hemorrhage and hemoptysis are uncommon in childhood, and the frequency with which they are encountered by the pediatric pulmonologist depends largely on the special interests of the center to which the child is referred. In those centers caring for children with cystic fibrosis or congenital heart disease, these will be by far the most common causes of hemoptysis. Other causes of hemoptysis are far less common, such as bleeding from localized lesions in the upper airway or tracheobronchial tree. Even less common is bleeding into the lungs as part of a systemic disease, usually with renal involvement (pulmonary-renal syndromes), such as systemic lupus erythematosis or Goodpasture's syndrome. Bleeding into the lungs in children with a bleeding diathesis probably only occurs in immunosuppressed children after transplantation. When no other cause is found for pulmonary hemorrhage, the presumed diagnosis is idiopathic pulmonary hemosiderosis. This review discusses the various causes of hemoptysis and pulmonary hemorrhage, and the appropriate investigations to aid in determining the correct diagnosis. The management and prognosis of idiopathic pulmonary hemosiderosis, based on cumulative experience from published reports, are considered in more detail.

Is clinical wheezing reliable as the endpoint for bronchial challenges in preschool children?

The present study was designed to compare the clinical finding of wheeze by auscultation with an objective evaluation by acoustic means at the endpoint of a bronchial challenge in preschool children. Challenges were undertaken using a tidal breathing method in 51 preschool children as part of the investigation of possible asthma. An electronic stethoscope was used for auscultation of each lung and for the simultaneous recording of the acoustic sonogram for analysis. In 24 children, the pediatrician determined that the challenge was positive, and in 22 of these, he heard wheezing at the endpoint of the challenge. In 2 children the challenge was considered positive, based on a modest fall in saturation. The acoustic record was scanned manually for presence of wheeze defined in terms of duration, and power spectrum without reference to auscultatory findings. In positive challenges, the mean wheeze rate was 28.1% (95% CI, 19.5-36.8%), while no wheeze was detected acoustically in negative challenges. Using a cutoff wheeze rate (duration of wheeze/duration of breath phase x100) of 10% for the whole group, clinical wheezing detected by the pediatrician had a sensitivity of 100% (no false negatives) and a specificity of 91%. In conclusion, the clinical observation of wheeze agrees very well with its detection by acoustic measurement at the endpoint of a bronchial challenge in preschool children.

Gavaging the infant lung.

An 8-month-old female infant was hospitalized for persistent bilateral infiltrates, failure to thrive, and tachypnea. An extensive diagnostic workup was negative, except for strong oil-red O staining of the white-turbid bronchoalveolar lavage fluid and borderline esophageal pH monitoring. Conservative treatment failed, and she was scheduled for gastrostomy and Nissen-fundoplication until the family physician found that the anxious mother was feeding the child forcibly, which caused chronic aspiration pneumonitis. The mother was given psychological support and was supervised, and the child recovered completely.

Exhaled nitric oxide is age-dependent in asthma.

We determined whether the exhaled nitric oxide (eNO) level in asthmatics is age-dependent. Eighty-seven asthmatic patients aged 2-41 years were studied. Hyperreactivity to adenosine 5'-monophosphate (AMP) was used to confirm asthma (

The effect of montelukast on bronchial provocation tests and exhaled nitric oxide levels in asthmatic patients.

BACKGROUND: Leukotriene antagonist therapy in asthmatic patients alleviates symptoms and improves exercise tolerance, however the effect of these drugs on bronchial provocation tests and exhaled nitric oxide levels are less clearly established. OBJECTIVE: To determine the effect of montelukast treatment on airway hyperresponsiveness to exercise, methacholine and adenosine-5'-monophosphate and on exhaled nitric oxide levels in steroid-naive asthmatics. METHODS: Following a 2 week run-in period, 20 mild to moderate asthmatics were enrolled in an open label 6 week trial of oral montelukast-sodium therapy. Bronchial hyperreactivity (exercise, methacholine and adenosine-5'-monophosphate challenges) and exhaled nitric oxide levels were measured before and after the 6 week period. RESULTS: Montelukast treatment resulted in a significant improvement in exercise tolerance: median delta FEV1 20.0% (range 0-50) prior to treatment vs. 15.0% (range 0-50) post-treatment (P = 0.029). A significant difference was also observed for exhaled NO following therapy: median NO 16.0 ppb (range 7-41) vs. 13.0 (range 4.8-26) (P = 0.016). No change was seen in baseline lung function tests (FEV1, MEF50) or in the bronchial responsiveness (PC20) for methacholine and adenosine-5'-monophosphate. CONCLUSIONS: This study demonstrates that the leukotriene antagonist montelukast-sodium reduces bronchial hyperreactivity in response to exercise and reduces exhaled nitric oxide levels but has little effect on bronchial responsiveness to methacholine and adenosine challenges.

Natural history of five children with surfactant protein C mutations and interstitial lung disease.

Interstitial lung diseases in infants and children are uncommon and may be caused by specific inborn errors of surfactant metabolism. Five children with open lung biopsy diagnosed interstitial lung disease were followed (mean of 27.2 years) and evaluated for surfactant protein gene mutations. Four of the children were originally diagnosed as desquamative interstitial pneumonitis and one as chronic interstitial pneumonitis. All had good response to chloroquine or hydroxychloroquine treatment for periods of 7-38 months. Lung function tests, incremental exercise tests, and rentgenological studies were performed in the children. Surfactant protein gene mutations were searched in all the patients and in part of their families. Three of the patients, aged now 32, 29, and 37 years, feel well and have normal lung function, while two of the patients, both females, aged 28 and 37 years, conduct normal activities of daily living, have healthy children but have clinical, physiological and rentgenological evidence of restrictive lung disease. All five patients were found to have surfactant protein C gene (SFTPC) mutations, three of them with the most common mutation (p.I73T) and the other two with new mutations of surfactant protein C gene (p.I38F and p.V39L). We conclude that detection of surfactant protein mutations should be attempted in all children presenting with interstitial lung disease. Furthermore, treatment with hydroxychloroquine should be considered in children with SFTPC mutations. Prospective evaluation of hydroxychloroquine therapy in a greater number of patients is needed.

Exercise-induced bronchoconstriction: celebrating 50 years.

This article examines in detail the history of more than half a century of investigations into elucidating the causation of exercise-induced bronchoconstriction. Despite earnest attempts by many researchers from many countries, answers to some pivotal questions await the next generation of investigators into exercise-induced bronchoconstriction.