Birth order, atopy, and symptoms of allergy and asthma among inner-city children attending Head Start in New York City.

BACKGROUND: In past research, children with older siblings were more likely than others to wheeze at age 2 years, but less likely by age 6 years. Higher infection transmission and a down-regulated allergic immune response as a result of these infections, respectively, were suggested as the causes. However, in a study of children aged 0-3 years in a low-income urban community in New York City, USA, with high asthma prevalence, we observed no birth-order effect. OBJECTIVE: To evaluate the association between birth order and atopy and respiratory symptoms in 4-year-old children attending Head Start programs in NYC. METHODS: Respiratory symptoms were assessed by questionnaire for 1005 children (mean age 4.0 years) living in high asthma prevalence neighbourhoods. Serum was collected from a subgroup of the children (n=494) and specific IgE responses to dust mite, cockroach, mouse, and cat allergens were measured. RESULTS: Prevalence of specific IgE (> or =0.35 IU/mL) did not differ significantly among first (35%), second (35%), and later-born children (28%) (P=0.23). Increasing birth order was associated with increasing prevalence of respiratory symptoms in the prior year, including wheeze (first 20%, second 27%, third or later 35%; P<0.001), being awakened at night by cough (28%, 33%, 38%; P=0.005), emergency department visits (14%, 17%, 21%; P=0.02) and hospitalizations for difficulty breathing (6.1%, 6.6%, 10%; P=0.04). The associations of birth order with respiratory symptoms were statistically significant only for the non-seroatopic children and those without an asthmatic parent. CONCLUSIONS: Non-seroatopic children with older siblings were more likely than those without older siblings to have respiratory symptoms at age 4 years. Although the stability of these associations over time remains to be determined, the differences in findings between this study and our previous NYC birth cohort study suggest that patterns of asthma development may vary even among low-income populations within the same city.

Asthma, body mass, gender, and Hispanic national origin among 517 preschool children in New York City.

BACKGROUND: Striking differences in asthma prevalence have been reported among Hispanic adults and children living in different cities of the USA. Prevalence is highest among those of Puerto Rican and lowest among those of Mexican origin. We hypothesized that body size would mediate this association. METHODS: Parents of children in New York City Head Start programs completed a questionnaire including demographic factors, health history, a detailed history of respiratory conditions, lifestyle, and home environment. Children's height and weight were measured in home visits. Logistic regression was used to model the association of asthma with body mass index percentile (<85th percentile, gender/age specific vs>or=85th percentile, gender/age specific), national origin, and other factors. RESULTS: Of 517 children at mean age of 4.0 +/- 0.6 years, 34% met the study criteria for asthma, and 43% were above the 85th percentile. Asthma was strongly associated with non-Mexican national origin, male gender, allergy symptoms, and maternal asthma, and marginally with body size. The odds of asthma among boys of non-Mexican origin was 5.9 times that among boys of Mexican origin [95% confidence interval (CI): 2.9-12.2]; the comparable odds ratio (OR) among girls was 1.8 (95% CI: 0.9-3.6). Body mass was associated with asthma among girls [OR = 2.0 (95% CI: 1.1-3.7)], but not boys [OR = 1.4 (95% CI: 0.8-2.6)]. CONCLUSIONS: The association of asthma with both body mass and national origin was gender-specific among the children in our study. Ours is one of the first studies to report on pediatric asthma in different Hispanic populations in the same city, by gender.

The application of Starling's law of capillary exchange to the lungs.

The forces governing the movement of water across the pulmonary capillaries were studied in 39 intact, spontaneously breathing dogs. A situation favoring the net movement of water out of the pulmonary capillaries was created by means of partial pulmonary venous obstruction (left atrial balloon catheter) followed by rapid saline hemodilution. A predetermined difference between pulmonary capillary and plasma colloid osmotic pressures was maintained for periods of 1 to 2 hours. Left atrial (P(LA)) and plasma colloid osmotic pressures (pi(pl)) were measured directly. The water content of the lungs was measured serially by an indicator-dilution technique, and at autopsy by drying the lungs. The rate of accumulation of lung water was measured in four groups of animals: in three of the groups, the capillary hydrostatic and colloid osmotic pressures were varied; in the fourth group, the right lymphatic duct was obstructed in addition. The average rate of water accumulation in the lungs varied in a nonlinear way with the level of the capillary hydrostatic-plasma colloid osmotic pressure difference and was unaffected by the level of the capillary hydrostatic pressure. At low levels of P(LA) - pi(pl), water accumulated in the lung at an average rate of 0.09 g per g dry lung per hour per mm Hg pressure difference. At higher levels of P(LA) - pi(pl) the average rate of accumulation was 0.22 g per g per hour per mm Hg DeltaP; in most of the experiments in this group water accumulated in the lungs slowly during the first 30 minutes of the test period and more rapidly as the period was extended. Obstruction of right lymphatic duct outflow did not alter the rate of water accumulation. Based on the control data of the present experiments, the pericapillary pressure in normal lungs is estimated to be of the order of - 9 mm Hg in the normal dog lung. The filtration coefficient for the pulmonary capillaries is estimated to be of the order of one-tenth to one-twentieth of that for canine muscle capillaries. The data of the present study indicate that edema formation in lung tissue cannot be defined solely in terms of intravascular forces, but may be governed to a significant degree by changes in pericapillary forces in the pulmonary interstitium.

Inhibition of angiotensin converting enzyme activity in cultured endothelial cells by hypoxia.

Endothelial cells in tissue culture degrade bradykinin and convert angiotensin I to angiotensin II. These are both functions of a single dipeptidyl hydrolase, angiotensin converting enzyme. Monolayer cultures were prepared from human, rabbit, pig, and calf vessels. Angiotensin converting enzyme activity was assessed by adding either bradykinin or angiotensin I to the cells in culture flasks, and measuring residual peptide over time by radioimmunoassay. Peptide degradation was inhibited by the specific converting enzyme inhibitor, SQ 20881. The flasks were equilibrated with varying hypoxic gas mixtures: hypoxia rapidly (less than 2 min) decreased enzyme activity and room air restored it as rapidly. The extent to which activity was reduced was a direct function of PO2 (r = 0.93, P less than 0.001), and there was no enzyme activity below a PO2 of 30 mm Hg. Four preparations were studied with respect to decrease in enzyme activity by hypoxia: (a) intact cells in monolayer, (b) sonicated cells, (c) sonicated cells from which converting enzyme was partially dissolved by a detergent, and (d) purified converting enzyme. Hypoxia had progressively less of an inhibiting effect on the enzyme activity of the preparations as the degree of cell integrity decreased. Hypoxia inhibits angiotensin converting enzyme activity in cultured endothelial cells, but the effect of hypoxia is not on the enzyme per se, but appears to be a unique characteristic of the endothelial cell.

Bradykinin production and increased pulmonary endothelial permeability during acute respiratory failure in unanesthetized sheep.

To investigate mechanisms of pulmonary edema in respiratory failure, we studied unanesthetized sheep with vascular catheters, pleural balloons, and chronic lung lymph fistulas. Animals breathed either a hypercapnic-enriched oxygen (n = 5) or a hypercapnic-hypoxic (n = 5) gas mixture for 2 h. Every 15 min blood gases, pressures, cardiac output, lymph flow (Qlym), plasma and lymph albumin (mol wt, 70,000), IgG (mol wt, 150,000), IgM (mol wt, 900,000), and blood bradykinin concentrations were determined. In both groups, cardiac output and pulmonary arterial pressures increased, whereas left atrial pressures were unchanged. Acidosis alone (arterial pH = 7.16, PaCO(2) = 81 mm Hg, PaO(2) = 250 mm Hg) resulted in a doubling of lymph flow, a small increase in protein flux, and a decrease in lymph to plasma protein concentration (L/P) ratio for all three proteins. Acidotic-hypoxic animals (arterial pH = 7.16, PaCO(2) = 84 mm Hg, PaO(2) = 48 mm Hg) tripled Qlym. In these animals the increase in lymphatic flux of albumin, IgG, and IgM was significantly (P < 0.05) greater than that seen in either the acidosis alone group or in animals where left atrial pressures were elevated (n = 5; P < 0.05). Also, their percent increase in flux of the large protein (IgM) was greater than for the small protein (albumin) (P < 0.05). With acidosis alone, only pulmonary arterial bradykinin concentration increased (1.27+/-0.25 ng/ml SE), whereas acidosis plus hypoxia elevated both pulmonary arterial bradykinin concentrations (4.83+/-1.14 ng/ml) and aortic bradykinin concentration (2.74+/-0.78 ng/ml). These studies demonstrate that hypercapnic acidosis stimulates in vivo production of bradykinin. With superimposed hypoxia, and therefore decreased bradykinin degradation, there is an associated sustained rise in Qlym with increased lung permeability to proteins.

Impaired angiotensin conversion and bradykinin clearance in experimental canine pulmonary emphysema.

Chronic hypoxic lung diseases are associated with abnormal blood pressure regulation. Because the lung is the principal site of angiotensin conversion and because hypoxia decreases converting enzyme activity, we examined whether angiotensin converting enzyme activity was impaired in lung disease. 12 dogs received a 6 wk course of aerosolized and intratracheal papain that produced moderate panlobular emphysema. These dogs and 24 control dogs were anesthetized and sampling catheters were placed under fluoroscopic control. Angiotensin conversion was measured by a blood pressure response bioassay. Pulmonary converting enzyme activity was also assessed by infusing bradykinin (BK) and using radioimmunoassay to measure the instantaneous clearance of BK and the concentration of BK in the pulmonary artery which first produced spillover of BK into left atrial blood. Angiotensin conversion was reduced in the emphysematous dogs to 81.1% (13.2 SD) from 92% (6 SD) in the control dogs (P < 0.01). Instantaneous clearance of BK in the emphysematous dogs was only slightly reduced (93%), despite reduction in their Pao(2) to 75 mm Hg, indicating that the greatest proportion of the perfused vascular bed was exposed to alveolar Po(2) of >90 mm Hg. However, the barrier to BK passage provided by the lung, and measured by the spillover level, was reduced (1/4) to (1/2) that observed in control animals. That the defect was promptly corrected by supplemental oxygen indicates that regional pulmonary vascular converting enzyme activity had been impaired by regional alveolar hypoxia, which permitted some peptide to pass through the lungs unmetabolized. Determination of peptide metabolism in the lungs may provide a useful measure of regional alveolar hypoxia and may lead to new ways of assessing lung injury.

Congenital failure of automatic control of ventilation, gastrointestinal motility and heart rate.

A new congenital syndrome characterized by the simultaneous failure of control of ventilation (Ondine's curse) and intestinal motility (Hirschsprung's disease) is reported in three infants, all of whom died in the first few months of life; two were siblings. Detailed studies in one also revealed markedly decreased esophageal motility and abnormal control of heart rate. In one infant, minute ventilation was lower in quiet than in REM sleep and lower in both states of sleep than in wakefulness. Although the mean inspiratory flow was decreased in quiet sleep, the hypoventilation resulted primarily from a decrease in respiratory frequency. Intravenous doxapram increased ventilation but did not reverse respiratory failure. Aminophyllin, progesterone, physostigmine and chlorpromazine did not change ventilation significantly; imipramine resulted in a significant decrease. Both long and short-term variability of the heart rate were markedly decreased when compared with the normal infant. Although neuropathologic studies postmorten did not reveal an anatomic defect, we postulate that a developmental abnormality in serotonergic neurons is responsible for this new syndrome.

Heart rate pattern during sleep in an infant with congenital prolongation of the Q-T interval (Romano-Ward syndrome).

Heart rate and the variability of the heart rate, indices of autonomic control, were studied during sleep in an infant with prolonged Q-T interval (Romano-Ward syndrome) and were compared to the heart rate and variability of heart rate in 18 normal infants studied at monthly intervals during the first four months of life. The overall variability and beat-to-beat variability in the infant with Romano-Ward syndrome were significantly below the median in the normal infants at each age and sleep state. This decrease in overall and beat-to-beat variability persisted after normalization by the absolute heart rate; however, the heart rate in the infant with Romano-Ward syndrome was not different from those in normal infants. These data suggest that the presence of a normal heart rate does not exclude abnormal autonomic activity; and in certain clinical situations, the variability of heart rate may be a more sensitive index of abnormal autonomic function than the heart rate itself.

Agenesis of the left lung and total anomalous pulmonary venous connection. Hemodynamic studies before and after complete surgical correction.

A female infant with unilateral pulmonary agenesis developed congestive heart failure dominated by symptoms of obstructive disease of the airways at 3 1/2 months of age. Cardiac catheterization revealed total anomalous pulmonary venous connection to the right atrium. Despite a massive left-to-right shunt with one pulmonary artery receiving the entire right ventricular output since birth, the patient's resting pulmonary vascular resistance was normal. Open heart surgery to repair the cardiac lesion was performed when the infant was four months of age. Subsequent studies revealed an excellent anatomic and functional repair, with normal pulmonary arterial pressures. One year following surgery, the child is asymptomatic and has normal growth and development.

Terbutaline in the treatment of status asthmaticus.

The effect of administration of terbutaline on the pulmonary and cardiovascular systems was studied in ten children with status asthmaticus. Terbutaline (0.01 to 0.04 mg/kg of body weight) was given subcutaneously in multiple doses. A significant decrease in respiratory rate and in arterial blood pressure, with no significant change in cardiac rate, was seen only after the first dose of terbutaline. There was a decrease in mean arterial carbon dioxide tension and an increase in mean arterial oxygen pressure. There was gross clinical improvement following administration of terbutaline in nine of the ten patients. One patient who failed to respond to administration of terbutaline also failed to respond to intravenously administered isoproterenol. We conclude that terbutaline is effective in the treatment of status asthmaticus, with only modest effects on the cardiovascular system.

Terbutaline in the treatment of acute asthma in childhood.

Forty-eight children with known asthma (ranging in age from 2 to 16 years) were studied during an acute attack. Each received either terbutaline or epinephrine subcutaneously in a random double-blind fashion. Measurement of heart rate, respiratory rate, and systemic arterial systolic and diastolic blood pressures and careful clinical assessment of obstruction of the airway were made before and at 15, 30, and 60 minutes after the administration of the drugs. Appreciable and significant clinical improvement was noted in 19 of the 24 patients in both groups and was of comparable magnitude. A small, but significant, increase in heart rate was noted in those patients requiring only one injection of terbutaline, suggesting that the drug's selectivity for the lung is relative not absolute. The present study demonstrates that terbutaline is an effective bronchodilator drug in acute childhood asthma.

Endothelial cell functions in the hemodynamic responses to stress.

ACE is a function of the endothelial cell that appears vital to integrative homeostatic physiology in stress. The endothelial cell, both in the lung and in systemic tissues, is uniquely situated to detect changes in ambient oxygen tension; thereafter, as exemplified by the effects of altered oxygen tension on ACE, the cell is capable of initiating changes that modulate its functions to reflect the altered physiologic state. Based upon extensive studies of endothelial cells propagated in tissue culture, these altered functions are rapid in onset, rapidly reversible, and quite closely correlated to PO2. Integrity of the endothelial cell membrane is necessary for the modulating changes to occur, and indeed, ACE purified from the cell is insensitive to changes in oxygen tension: it is the cell, not the enzyme, that responds to changes in oxygen tension (FIGURE 5). It is important to emphasize the interdependent nature of the several vasoactive systems. The kallikrein-kinin system, in addition to its putative role in blood pressure regulation, is an intimate component of both the coagulation and fibrinolysis plasma protease cascades. The sympathetic nervous system has multiple points of interdigitation in both the kallikrein-kinin and the renin-angiotensin systems; high levels of epinephrine stimulate renin release and activate both plasma and tissue kallikrein. In turn, both of the vasoactive peptides of these systems, bradykinin and angiotensin II, stimulate epinephrine production from the adrenal medulla. Angiotensin II enhances the potency of norepinephrine released from postganglionic sympathetic nerve endings, increasing alpha-adrenergic tone. In addition, multiple interactions have been described between angiotensin II and bradykinin and the formation of prostaglandins by endothelial cells. Preliminary data indicate that the potency of these peptides in causing prostanoid release is, as might be expected, closely correlated to ACE activity, which itself is a function of ambient PO2. These multiple interactions are diagrammed in FIGURE 9. It is noteworthy that the two fundamental regulators of the circulation, pH and PO2, can be shown to interact at the most basic level with endothelial cell function.

Systemic hemodynamics affecting cardiac output during hypocapnic and hypercapnic hypoxia.

Systemic hemodynamic adjustments involved in the control of cardiac output (CO) were examined in chronically instrumented unanesthetized sheep inhaling gas mixtures resulting in hypocapnic hypoxia (H) [arterial pH (pHa) = 7.53, arterial partial pressure of O2 (Pao2) = 30 Torr, arterial partial pressure of CO2 (Paco2) = 29 Torr] or hypercapnic hypoxia (HCH) (pHa = 7.14, Pao2 = 34 Torr, Paco2 = 72 Torr) for 1 h. H (n = 7) and HCH (n = 6) resulted in 26% and 61% increases in CO, respectively, and mean systemic arterial pressure rose to a greater extent during HCH. Both H and HCH resulted in increased blood flow (microsphere method) to the peripheral systemic circulation including the brain, heart, diaphragm, and nonrespiratory skeletal muscle (the latter blood flow increased 120% during H and 380% during HCH). Gastrointestinal and renal blood flow remained unchanged during H and HCH. Transit time of green dye from the pulmonary artery to regional veins in the hindlimb and intestine was 5.0 and 8.2 s, respectively, during base-line conditions and remained unchanged with HCH. During HCH, regional O2 consumption increased 274% for the hindlimb and decreased 39% for the intestine. Total catecholamines rose 250% during H and 3,700% during HCH. During hypocapnic and hypercapnic hypoxia, CO is augmented in part by systemic hemodynamic adjustments that include a redistribution of blood flow and a translocation of blood volume to the fast transit time peripheral systemic circuit. The sympathetic nervous system may play an important role in mediating these systemic hemodynamic adjustments.

Pediatric HIV infection in its second decade--the changing pattern of lung involvement. Clinical, plain film, and computed tomographic findings.

The changing pattern of pediatric HIV infection is illustrated in this article with plain films and computed tomographic scans. Today, vertical transmission from infected mothers results in HIV infection of exposed infants in about one third of pregnancies. Although the high mortality with catastrophic illnesses such as Pneumocystis carinii pneumonia seen in early life appears to be decreasing, chronic illness with pulmonary involvement due to diffuse lymphocytic infiltrative syndromes continues. Lymphocytic interstitial pneumonitis (LIP) has evolved in some patients to cystic lung disease and bronchiectasis. There are increasing numbers of patients infected with Mycobacterium. Masses seemingly of smooth muscle origin, thought to be leiomyosarcoma are appearing; they may be pseudotumors related to concomitant Mycobacterium avium intracellulare infection.

Respiratory diseases in the first year of life in children born to HIV-1-infected women.

Our objective was to describe the respiratory complications, clinical findings, and chest radiographic changes in the first year of life in infected and uninfected children born to HIV-1-infected women. We prospectively followed a cohort of 600 infants born to HIV-1-infected women from birth to 12 months in a multicenter study. Of these, 93 infants (15.5%) were HIV-1-infected, 463 were uninfected, and 44 were of unknown status prior to death or loss to follow-up. The cumulative incidence ( +/- SE) of an initial pneumonia episode at 12 months was 24.1 +/- 4.7% in HIV-1-infected children compared to 1.4 +/- 0.6% in HIV-1-uninfected children (P < 0.001). The rate of Pneumocystis carinii pneumonia (PCP) was 9.5 per 100 child-years. The HIV-1 RNA load was not higher in the group that developed pneumonia in the first year vs. those who did not. Children who developed lower respiratory tract infections or PCP had increased rates of decline of CD4 cell counts during the first 6 months of life. Lower maternal CD4 cell counts were associated with higher rates of pneumonia, and upper and lower respiratory tract infections. The rates of upper respiratory tract infection and bronchiolitis/reactive airway disease in infected children were not significantly different than in uninfected children. At 12 months, significantly more HIV-1-infected than uninfected children had tachypnea and chest radiographs with nodular and reticular densities. There was no relationship between cytomegalovirus infection in the first year of life and radiographic changes or occurrences of pneumonia. In conclusion, despite a low incidence of PCP, rates of pneumonia remain high in HIV-infected children in the first year of life. The incidence of pneumonia in uninfected infants born to HIV-1-infected mothers is low. Chest X-ray abnormalities and tachypnea suggest that subacute disease is present in infected infants. Further follow-up is warranted to determine its nature.

Communication within low income families and the management of asthma.

This study examines the effects of communication between low income urban parents and children about a chronic disease on the extent to which parent and child effectively manage the illness. Four asthma communication factors were identified by principal component analysis. We found that mothers whose preferred language was Spanish, and families who were not receiving public assistance, communicated more frequently about asthma in general. Spanish speaking mothers and their children communicated more about potential home treatments for asthma, and the more adults in the household the less there was communication about the need for emergency services for asthma. Mothers who preferred to speak Spanish had higher levels of management of the most recent asthma attack. Those whose children communicated with them about asthma in general were higher level managers. Children who influenced their parents' decisions about school attendance, and those whose mothers were more highly educated, had higher levels of asthma attack management. More educated mothers, ones whose children were younger at the time of the onset of asthma, and one who received public assistance, were more involved "in general" in their child's asthma care.

Managing better: children, parents, and asthma.

To evaluate a health education program to improve family management of asthma, 310 children with asthma and their 290 parents were randomly assigned to a program or control group. Program families participated in health education designed to resolve specific management problems and build self-confidence in the ability to manage asthma. Following education, program parents scored better on an asthma self-management index than parents in the control group (+1.57 versus -0.83, P less than 0.0001). Program parents also scored better on two subindices of the self-management index: attack management (+0.87 vs. +0.42, P less than 0.05) and preventive measures (+0.42 vs. -0.35, P less than 0.05). Also, program parents reported significantly more use of guidelines to determine appropriate levels of physical activity for children. Following education, program children reported more use of three management steps than control children: productive cough or postural drainage (59% vs. 35%, P less than 0.004), breathing and relaxation exercises (80% vs. 65%, P less than 0.05), and attempts to stay calm (12% vs. 2%, P less than 0.05). Program children reported significantly less worry than control children about the limitations asthma imposes and about making mistakes at school.

Self-regulating childhood asthma: a developmental model of family change.

This article tests a model of self-regulatory development in which families' cognitive beliefs and behavioral skills for managing asthma symptoms emerge in four successive phases: asthma symptom avoidance, asthma acceptance, asthma compliance, and asthma self-regulation. Confirmatory factor analyses revealed that the hypothesized multiphase model provided the best factorial fit for phase items. Subsequent Guttman analyses of the families' phase scores revealed a high degree of sequential ordering. Finally, trend analyses of family phase differences revealed a significant negative linear relation with measures of asthma severity and a significant positive linear relation with physician care and concern measures, asthma regulatory measures, and beliefs in Western biomedical practices. Despite receiving primary care for asthma at a major metropolitan university hospital, 83% of the sample were classified as precompliant. The phase model of asthma self-regulatory development offers a qualitative approach for investigating the psychological determinants of asthma self-regulatory behavior.

Can children teach their parents about asthma?

The Open Airways for Schools (OAS) program has been shown to improve the self-management skills and health outcomes of students with asthma in Grades 3 to 5. This report examines the impact of OAS on students' parents. Because pilot studies showed that parental attendance at school-based sessions was low, the authors held six sessions at school for children and gave children homework assignments to complete with parents at home to teach parents about asthma and build support for children's self-management efforts. Analysis of 1-year follow-up data showed that children's participation in OAS was a significant predictor of parental self-management skills (p <.03) and that OAS children's communication was more strongly associated than controls' with parents' self-management (p = .05). The findings show that health education activities brought home from school by children can positively influence parents' self-management of a complex chronic disease such as asthma.

A scale for Assessing Health Care Providers' Teaching and Communication Behavior regarding asthma.

Partnership between health care providers and patients is important for controlling illness. A limited number of studies show how to assess health professionals' communication and partnering behavior. The relationship between these aspects of professional behavior and enhanced management of disease by patients has received little empirical study. The research reported here developed a Health Care Providers' Teaching and Communication Behavior (TCB) scale for assessing the teaching and communication behavior of clinicians treating patients with asthma. Such a tool is needed for research related to provider-patient relationships and for evaluation of professionals' performance.