Cough during infancy and subsequent childhood asthma.

OBJECTIVES: Wheezing in infancy has been associated with subsequent asthma, but whether cough similarly influences asthma risk has been little studied. We sought to determine whether prolonged cough and cough without cold in the first year of life are associated with childhood asthma. METHODS: Participants in the Infant Immune Study, a non-selected birth cohort, were surveyed 7 times in the first 9 months of life regarding the presence of wheeze and cough. Cough for more than 28 days was defined as prolonged. Parents were asked at 1 year if the child ever coughed without a cold. Asthma was defined as parental report of physician diagnosis of asthma, with symptoms or medication use between 2 and 9 years. Logistic regression was used to assess adjusted odds for asthma associated with cough characteristics. RESULTS: A total of 24% (97) of children experienced prolonged cough and 23% (95) cough without cold in the first 9 months, respectively. Prolonged cough was associated with increased risk of asthma relative to brief cough (OR 3.57, CI: 1.88, 6.76), with the risk being particularly high among children of asthmatic mothers. Cough without cold (OR 3.13, 95% CI: 1.76, 5.57) was also independently associated with risk of childhood asthma. Both relations persisted after adjustment for wheeze and total IgE at age 1. CONCLUSIONS AND CLINICAL RELEVANCE: Prolonged cough in infancy and cough without cold are associated with childhood asthma, independent of infant wheeze. These findings suggest that characteristics of cough in infancy are early markers of asthma susceptibility, particularly among children with maternal asthma.

Child day care, smoking by caregivers, and lower respiratory tract illness in the first 3 years of life. Group Health Medical Associates.

BACKGROUND: Day-care attendance has been associated with an increased risk of hospitalization for lower respiratory tract illnesses (LRIs). This study examines, in a health maintenance organization population of children, the associations between child day care and the occurrence of LRIs in the first 3 years of life. Smoking by caregivers and a possible protective effect of longer day-care enrollment in relation to LRIs are also addressed. METHODS: Information on day-care arrangements was elicited from 1006 parents of infants for five age intervals in the first 3 years of life: birth through 3 months, 4 to 6 months, 6 to 12 months, 1 to 2 years, and 2 to 3 years. Data on LRIs in the first 3 years of life were recorded by pediatricians at the time of the acute illnesses. RESULTS: After controlling for other risk factors, the presence of three or more unrelated children in the care setting was associated with significant risks of LRI of up to twofold or more from 4 months of age to 3 years. Type of care setting was not a significant risk factor during this time period. In the third year of life, the risk of wheezing LRI in the presence of a smoking caregiver was more than threefold for those in another residential home setting. No significant protective effect against LRIs in the third year of life associated with longer prior day-care enrollment was demonstrated. CONCLUSION: The presence of three or more unrelated children in the care setting and the presence of a smoking caregiver were significant independent risk factors for LRIs during the first 3 years of life. Prolonged day-care did not protect against LRIs in the third year of life.

Feasibility of using unattended polysomnography in children for research--report of the Tucson Children's Assessment of Sleep Apnea study (TuCASA).

STUDY OBJECTIVES: The Tucson Children's Assessment of Sleep Apnea study (TuCASA) is designed to investigate the prevalence and correlates of objectively measured sleep-disordered breathing in pre-adolescent children. This paper documents the methods and feasibility of attaining quality unattended polysomnograms in the first 162 TuCASA children recruited. DESIGN: A prospective cohort study projected to enroll 500 children between 5 and 12 years of age who will undergo unattended polysomnography, neurocognitive evaluation, and physiological and anatomical measurements thought to be associated with sleep-disordered breathing. SETTING: Children are recruited through the Tucson Unified School District. Polysomnograms and anthropometric measurements are completed in the child's home. PARTICIPANTS: Of the 157 children enrolled in TuCASA, there were 100 children (64%) between 5-8 years old and 57 children (36%) between the ages of 9 to 12. There were 74 (47%) Hispanic children, and 68 (43%) female participants. INTERVENTIONS: N/A. MEASUREMENTS & RESULTS: Technically acceptable studies were obtained in 157 children (97%). The initial pass rate was 91%, which improved to 97% when 9 children who failed on the first night of recording completed a second study which was acceptable. In 152 studies (97%), greater than 5 hours of interpretable respiratory, electroencephalographic, and oximetry signals were obtained. The poorest signal quality was obtained from the chin electromyogram and from the combination thermister/nasal cannula. Parents reported that 54% of children slept as well as, or better than usual, while 40% reported that their child slept somewhat worse than usual. Only 6% were observed to sleep much worse than usual. Night-to-night variability in key polysomnographic parameters (n=10) showed a high degree of reproducibility on 2 different nights of study using identical protocols in the same child. In 5 children, polysomnograms done in the home were comparable to those recorded in a sleep laboratory. CONCLUSIONS: The high quality of data collected in TuCASA demonstrates that multi-channel polysomnography data can be successfully obtained in children aged 5-12 years in an unattended setting under a research protocol.

Sleep-disordered breathing, pharyngeal size and soft tissue anatomy in children.

We tested the hypothesis that pharyngeal geometry and soft tissue dimensions correlate with the severity of sleep-disordered breathing. Magnetic resonance images of the pharynx were obtained in 18 awake children, 7-12 yr of age, with obstructive apnea-hypopnea index (OAHI) values ranging from 1.81 to 24.2 events/h. Subjects were divided into low-OAHI (n = 9) and high-OAHI (n = 9) groups [2.8 +/- 0.7 and 13.5 +/- 4.9 (SD) P < 0.001]. The OAHI correlated positively with the size of the tonsils (r2 = 0.42, P = 0.024) and soft palate (r2 = 0.33, P = 0.049) and inversely with the volume of the oropharyx (r2 = 0.42, P = 0.038). The narrowest point in the pharyngeal airway was smaller in the high-compared with the low-OAHI group (4.4 +/- 1.2 vs. 6.0 +/- 1.3 mm; P = 0.024), and this point was in the retropalatal airway in all but two subjects. The airway cross-sectional area (CSA)-airway length relation showed that the high-OAHI group had a narrower retropapatal airway than the low-OAHI group, particularly in the retropalatal region where the soft palate, adenoids, and tonsils overlap (P = 0.001). The "retropalatal air space," which we defined as the ratio of the retropalatal airway CSA to the CSA of the soft palate, correlated inversely with the OAHI (r2 = 0.49, P = 0.001). We conclude that 7- to 12-yr-old children with a narrow retropalatal air space have significantly more apneas and hypopneas during sleep compared with children with relatively unobstructed retropalatal airways.

Serum/saliva correlations for theophylline in asthmatics.

Theophylline levels in mixed saliva (both stimulated and unstimulated) were compared with total and free (unbound) serum theophylline levels in 28 asthmatic outpatients using theophylline regularly. Stimulated saliva predicted both total and unbound serum theophylline concentrations within +/- 1 microgram/mL in 62.5% and 92.9%, respectively, of the samples examined. In addition, the total serum levels could be used to predict unbound serum concentrations to within +/- 1 mg/L in 100% of the cases that were examined. These results indicate that saliva levels predict the unbound serum theophylline levels with greater accuracy and precision than they predict total serum theophylline levels. In addition, total serum levels can be used to reliably predict unbound serum levels. The use of mixed stimulated saliva is recommended as a reliable non-invasive method for monitoring unbound serum theophylline levels. The therapeutic range for saliva, which corresponds to the accepted total serum concentration range of 10-20 mg/L, is approximately 5.6-11.3 mg/L.

Infants with upper respiratory illnesses have significant reductions in maximal expiratory flow.

We studied maximal expiratory flows at functional residual capacity (VmaxFRC) obtained by use of the chest compression technique in 9 infants who had signs of upper respiratory illness (URI) at the time of testing, and in 9 infants who were symptom-free but whose parents reported they had a URI in the previous month. When compared to 109 infants with no URI, infants with current URI had 40% lower VmaxFRC (mean +/- SD: 125.7 +/- 54.5 mL/s vs. 73.6 +/- 53.6 mL/s; P less than 0.01). Infants with a past URI had mean values for VmaxFRC (120.2 +/- 50.2 mL/s) that were not significantly different from those of infants with no URI. Changes in the shape of the flow-volume loop analogous to those reported in infants with lower airway obstruction were also noticed in infants with current URI. These findings suggest that, as in older children and adults, clinically unapparent alterations in lower airway function occur during URI in infants.

Circulating levels of tumor necrosis factor and interleukin-1 in cystic fibrosis.

To assess the role of tumor necrosis factor (TNF) and interleukin-1 (IL-1) in the pathophysiology of cystic fibrosis (CF)-associated growth failure/cachexia and lung disease we measured height, weight, triceps skin fold, forced vital capacity, forced expiratory volume in 1 second, and plasma levels of TNF, interleukin-1-alpha (IL-1 alpha), interleukin-1-beta (IL-1 beta), and alpha-1-antitrypsin (A1AT) in 12 patients with CF, and in 12 age- and gender-matched healthy controls. The patients as a group had significantly lower values for the anthropomorphic measurements and lung function parameters as compared to controls. They also had higher circulating levels of A1AT than controls. TNF, however, was detected less frequently in patients than in controls. Neither group had detectable levels of circulating IL-1 alpha or IL-1 beta, which is consistent with the observation that CF patients infrequently present with fever. Potential explanations for these findings include compartmentalization of secreted TNF/IL-1, altered regulation of TNF/IL-1 secretion as a result of the chronic inflammatory state seen in CF, or increased degradation of TNF/IL-1, also a result of chronic inflammation. The role of these cytokines in the pathophysiology of CF remains unclear, but should be explored further; however it seems unlikely that circulating TNF plays a role in the growth failure/cachexia associated with CF.

Airway responsiveness to cold, dry air in normal infants.

Reactive airway disease may be related to genetic, infectious, and environmental factors. The latter two have been well documented, but there are no data on nonspecific airway responsiveness in normal infants prior to any insult to the respiratory tract. We measured forced expiratory flow by the thoracic compression technique and lung volume in 30 normal infants before and after challenge with cold, dry air (CDA) and compared the results with those in 12 infants who did not receive CDA challenge. As a group, infants challenged with CDA had a mean decrease in VmaxFRC of 17.9 +/- 24.1% SD. This was significantly different (P less than 0.01) from the lack of change (+ 1.3 +/- 18.1% SD) seen in the control group. We conclude that nonspecific airway reactivity may exist from early infancy and may predate any known lung injury. The relationship of this airway responsiveness to subsequent reactive airway disease and other respiratory illnesses is unknown and requires longitudinal study.

The relation between physician-diagnosed sinusitis, asthma, and skin test reactivity to allergens in 8-year-old children.

The purpose of this study was to assess the prevalence of sinusitis in a nonselected sample of children, and the relation of sinusitis to allergic rhinitis (AR), atopy, asthma, and cough in the same population sample. Of 1246 children enrolled at birth in the Tucson Children's Respiratory Study, 835 were studied at a mean age +/-SD of 8.6 +/- 0.7 years. Questionnaires asking about MD-Sinusitis, MD-AR, MD-Asthma, and cough were completed by parents. Skin tests for seven common aeroallergens in the Tucson area had been performed in 630 of the participating children at the mean age +/-SD of 6.3 +/- 0.9 years. Prevalence of MD-Sinusitis was 13.1%; 78% of subjects with MD-Sinusitis also had MD-AR. Detailed analysis of the relation between MD-Sinusitis and individual environmental allergens tested for showed that only a response to Bermuda grass pollen was significantly associated with MD-Sinusitis after controlling for MD-AR [adjusted odds ratio 2.3 (95% CI 1.2-4.3)]. Having MD-Sinusitis was also significantly associated with MD-Asthma and cough [odds ratios 3.0 (95% CI 1.8-5.2)] and 2.5 (95% CI 1.6-3.8), respectively]. However, logistic regression demonstrated that, after controlling for MD-AR and skin test reactivity, MD-Sinusitis was no longer significantly associated with MD-Asthma or cough. We conclude that MD-Sinusitis is a common condition in childhood. The main independent risk factors in our community for MD-Sinusitis were grass pollen and current MD-AR. MD-Sinusitis was not associated with MD-Asthma or with cough after controlling for skin test reactivity and for MD-AR.

Patterns of medical practice in cystic fibrosis: part I. Evaluation and monitoring of health status of patients. Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis.

This report characterizes patterns of evaluation and monitoring of the health status of patients with cystic fibrosis (CF) as observed in the Epidemiologic Study of Cystic Fibrosis (ESCF), and compares these practices to published guidelines. All patients (18,411) who enrolled in ESCF at 194 study sites in the United States and Canada from December 1, 1993 to December 31, 1995 were considered for study. Patients enrolled before January 1, 1995 with >/=1 healthcare encounters during 1995 (12,631) were included in the analysis. Patients enrolled after January 1, 1995 (5,266), or who died (354), withdrew from the study (128), or were lost to follow-up (21) were excluded. Frequency of encounters (outpatient and hospital), spirometry, respiratory tract cultures, and chest radiographs were recorded during a 1-year period (1995) and analyzed by gender, age, severity of lung disease, and presence of any Pseudomonas species in the respiratory tract. The 12,631 patients had 53,024 outpatient visits. In 57.5% of patients, the recommended criteria of >/=4 total visits per year were met. Only 27.4% of all patients had >/=4 routine visits; 3.1% had only sick visits, and 59.0% had no sick visits. One third (34.6%) were hospitalized at least once, for a total of 8,561 hospitalizations. Older patients with lower pulmonary function and Pseudomonas in their respiratory tract had fewer routine visits and more sick visits, and were hospitalized more than were younger patients. In three fourths (75.8%) of patients the recommended criterion of two spirometry assessments per year was met, whereas in 79.3% the criterion of one culture was met, and in 68.3% the criterion of one radiograph/year was met. We conclude that in the majority of CF patients, the recommended criteria for routine evaluation and monitoring were met. However, in a rather substantial number they were not. An increase in the utilization of healthcare resources was observed in patients with more severe disease. This information will help to establish benchmarks for future quality assessment programs.

Patterns of medical practice in cystic fibrosis: part II. Use of therapies. Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis.

This report describes the prescribing pattern of therapeutic interventions in the management of patients with cystic fibrosis (CF), as observed in the Epidemiologic Study of Cystic Fibrosis (ESCF). Use of 20 therapies by 12,622 patients was recorded from each health care encounter (53,024 outpatient visits and 8,561 hospitalizations) during a 1-year period (1995), and analyzed by gender, age, severity of lung disease, and presence of any Pseudomonas species in the respiratory tract. The percentage of patients using the following pulmonary therapies was observed (in descending order): airway clearance techniques (88.2%); inhaled bronchodilators (82.2%); oral antibiotics (excluding quinolones) (68. 2%); dornase alfa (52.9%); intravenous antibiotics (34.4%); oral quinolones (34.4%); inhaled antibiotics (34.3%); mast cell stabilizers (29.5%); inhaled corticosteroids (25.9%); oral corticosteroids (17.1%); oral bronchodilators (16.2%); oxygen (8. 1%); inhaled mucolytic agent acetyl cysteine (6.5%); and diuretics (1.4%). The percentage of patients using nutritional therapies was: pancreatic enzymes (96%); oral nutritional supplements (31.1%); enteral nutrition (7.3%); and parenteral nutrition (0.7%). The percentage of patients using other therapies was: nonsteroidal anti-inflammatory drugs (7.9%); and insulin or oral hypoglycemic agents (6.1%). The general trend was for therapies to be used more by older patients, those with lower pulmonary function, and by those with Pseudomonas in their respiratory tract. Exceptions to this trend occurred for airway clearance, oral antibiotics, mast cell stabilizers, and pancreatic enzymes. Four therapies (oral nutritional supplements, parenteral nutrition, diuretics, and pancreatic enzymes) were used more by males than females. However, there was no gender difference for this group of therapies on pulmonary or nutritional status.

Epidemiologic study of cystic fibrosis: design and implementation of a prospective, multicenter, observational study of patients with cystic fibrosis in the U.S. and Canada.

Cystic fibrosis (CF) is a complex illness characterized by chronic lung infection leading to deterioration in function and respiratory failure in over 85% of patients. An understanding of the risk factors for that progression and the interaction of these factors with current therapeutic strategies should materially improve the prevention of this progressive lung disease. The Epidemiologic Study of Cystic Fibrosis (ESCF) was therefore designed as a multicenter, longitudinal, observational study to prospectively collect detailed clinical, therapeutic, microbiologic, and lung function data from a large number of CF treatment sites in the U.S. and Canada. The ESCF also serves an important role as a phase-IV study of dornase alfa. To be eligible for enrollment, subjects must have the diagnosis of CF and receive the majority of their care at an ESCF site. In this paper, the authors present the ESCF study design in detail. Further, enrollment data collected at 194 study sites in 18,411 subjects enrolled from December 1, 1993 to December 31, 1995 are presented in summary form. This comprehensive study is unique in the detail of clinical data collected regarding patient monitoring and therapeutic practices in CF care. Two companion articles present data regarding practice patterns in cystic fibrosis care, including data on resource utilization and prescribing practices.

On the creation of 'problem' patients.

Recent debates regarding clinical transactions oppose a macro-level approach which emphasizes political, economic and institutional forces, and those analysts who consider patient perceptions regarding illness to be major influences on the outcome of clinical encounters. This paper utilizes both approaches to illuminate the interactions between medical personnel and 'problem patients'. The macro-level approach draws attention to the way power is negotiated and expressed in clinical interactions, and to medicalization that gives priority to medical values and condemns patients who do not act in accord with these values. The patient belief approach explores one of the major weapons in the struggle for control, the disease model of illness. Use of both approaches permits a better understanding of clinical medicine in these problematic interactions.

The chronic bronchitis complex in children.

In childhood, a clear definition, etiology, natural history, therapy, and prognosis have not been described for chronic bronchitis. In fact, its validity as a single disease entity is in question. This article offers a pragmatic approach by considering "chronic bronchitis" as a pathophysiologic description of a symptom complex that results from the interaction of both intrinsic and extrinsic factors. In this schema, the physician should rule out more specific diagnoses and prevent further airway disease by limiting exogenous causes of airway damage and treating identifiable endogenous ones.

Risk factors for developing wheezing and asthma in childhood.

Wheezing lower respiratory tract illness in infancy and asthma share the clinical findings of wheezing and respiratory distress. Although the link between wheezing lower respiratory tract illness in infancy and the subsequent development of asthma is a limited one, both conditions do share some common risk factors, including exposure to environmental tobacco smoke, difficult living conditions (low socioeconomic class, crowding, allergen exposure), and increased risk in males. The impact of baseline lung function on wheezing lower respiratory tract illness risk is substantial and may be independent of airway reactivity. In contrast, the development of chronic airway inflammation mediated by allergic sensitization plays a central role in the development of persistent asthma. Although the endogenous risks for these two outcomes may be fixed, it is clear that caregivers may help to reduce or eliminate the exogenous risks listed earlier by parental education and improvement of the living conditions of young children.

Pulmonary function in infants and children.

The assessment of pulmonary function in infants and children with lung disease can add substantially to their diagnosis and management. This article is a practical review of techniques such as peak flow measurement and spirometry which can be performed in the home or office setting. More complex methods such as airway challenge and infant lung function testing techniques also are discussed.

Wrist kinematics during pitching. A preliminary report.

A computerized hand and wrist motion analysis system was modified to capture data at a rate of up to 1000 Hz. Using this system, wrist flexion and extension data were collected on five right-handed professional pitchers (75 pitches). A wrist position versus time graph was generated for each pitch. The pitch data produced a reproducible analysis of motion for the majority of the pitches regardless of pitcher. Based on the graphic display of data points, four phases of wrist motion during a pitch were identified. The first phase is the cocking phase, or the motion of the wrist as it moves into maximum extension. This is then followed by the most explosive phase, the acceleration phase, which represents ball propulsion. At ball release, the wrist progresses through flexion and there is a consistent decrease in wrist velocity, known as the deceleration phase. Finally, there is the recovery phase, or the return of the wrist toward neutral. Average values for wrist range of motion, length of phase, and angular velocity (degrees per second) were calculated for each phase of the pitch. This study represents a major step toward quantifying motion of the wrist during a pitch. The ability to quantify this motion may prove valuable in the assessment of throwing athletes after injury and rehabilitation.

Acute hand and wrist injuries in athletes: evaluation and management.

Acute hand and wrist injuries in the athlete constitute a unique orthopaedic challenge. Because of the particular demands on the athlete (e.g., financial implications, coaching and administration pressures, self-esteem issues), a specialized management approach is often necessary. Common sites of injury include the ulnar collateral ligament of the thumb metacarpophalangeal joint, proximal interphalangeal joint, metacarpals and phalanges, scaphoid, hamate, and distal radius. Treatment of these injuries varies depending on the patient's age, sport, position played, and level of competition, but departures from standard practice as regards surgery, rehabilitation, and return to competition should never compromise care.

Foreign bodies in the hand.

A prospective study was carried out on 164 consecutive cases presenting at the Accident Department with foreign bodies in the hand. The distal segment of the digits was the commonest site. The late, symptomatic presentation of patients, together with the development of symptoms in patients managed conservatively indicate that foreign bodies should be removed. General anaesthesia is rarely required, but an effective "block" with a tourniquet is necessary, as infiltration anaesthesia has a high failure rate, and secondary exploration a high complication rate. Glass fragments are almost always visible on plain x-rays.

A rapid and specific high-performance liquid chromatographic assay for theophylline in biological fluids.

A rapid, specific high-performance liquid chromatographic analysis of theophylline in plasma, serum, and saliva is described. Proteins present in the biological samples are precipitated with 6% perchloric acid and the clear supernatant is chromatographed on a reversed-phase column. Only 100 microL of serum is required and concentrations as low as 0.07 micrograms/mL can be measured accurately. Other xanthines do not interfere in the assay. Within- and between-day variation is less than or equal to 2.2%. The method shows less bias and greater precision than the TDx (Abbott Diagnostics) procedure commonly used in clinical laboratories.