Referral indications and prevalence of sleep abnormalities in children with early onset scoliosis.

This study describes the utility of overnight sleep studies in children with early onset scoliosis (EOS). Children with EOS have diminished respiratory reserve which is associated with abnormal breathing and sleep quality in children. Currently, there are no criteria for referral of these children to evaluate breathing during sleep or data on the use of sleep treatments as part of their supportive care. A review of the 159 patients with EOS who were followed at a single institution from 2003 to 2016 identified 68 who underwent overnight polysomnograms (PSGs). Sixty-five of 68 (96%) had elevated apnea-hypopnea index (AHI) and a majority (56%) were prescribed nighttime respiratory support. A majority of young children (< 5 years) with PSG were referred for a history of snoring, apnea, or restless sleep; all 30 had abnormal PSGs. Twenty-seven (90%) had nighttime hypoxemia (nadir oxygen saturation values < 92%). Eighteen (60%) were referred to otolaryngology, of whom 11 (37%) subsequently underwent tonsil and/or adenoid removal. In older children (≥ 5 years), those referred for PSGs had more severe restrictive chest wall disease [lower forced vital capacity (FVC) values] than those who were not sent for PSG. Correlation between FVC and apnea-hypopnea index, however, was not significant. Pre-operative coronal curve magnitude did not strongly correlate with nadir SaO2 or AHI in either age group. These results suggest that sleep studies are underutilized in the management of children with EOS. Inadequate and poor-quality sleep adversely affects growth, behavior, and cognitive function in children. This study suggests that screening for sleep abnormalities should be incorporated into assessment and treatment of more patients with EOS.

Lung disease in indigenous children.

Children in indigenous populations have substantially higher respiratory morbidity than non-indigenous children. Indigenous children have more frequent respiratory infections that are, more severe and, associated with long-term sequelae. Post-infectious sequelae such as chronic suppurative lung disease and bronchiectasis are especially prevalent among indigenous groups and have lifelong impact on lung function. Also, although estimates of asthma prevalence among indigenous children are similar to non-indigenous groups the morbidity of asthma is higher in indigenous children. To reduce the morbidity of respiratory illness, best-practice medicine is essential in addition to improving socio-economic factors, (eg household crowding), tobacco smoke exposure, and access to health care and illness prevention programs that likely contribute to these issues. Although each indigenous group may have unique health beliefs and interfaces with modern health care, a culturally sensitive and community-based comprehensive care system of preventive and long term care can improve outcomes for all these conditions. This article focuses on common respiratory conditions encountered by indigenous children living in affluent countries where data is available.

Exhaled nitric oxide predicts persistence of wheezing, exacerbations, and decline in lung function in wheezy infants and toddlers.

BACKGROUND: There are limited data assessing the predictive value of fraction of exhaled nitric oxide (FENO ) for persistence of wheezing, exacerbations, or lung function change over time in infants/toddlers with recurrent wheezing. OBJECTIVES: In an ongoing longitudinal cohort of infants and toddlers with recurrent wheezing, we compared predictive values of single-breath FENO (SB-FENO ), tidal-breathing mixed expired FENO (tidal-FENO ), bronchodilator responsiveness (BDR) and the Castro-Rodriquez Asthma Predictive Index (API) for persistence of wheezing, exacerbations and lung function change through age 3 years. METHODS: Enrolment forced expiratory flows and volumes infant pulmonary function tests (iPFTs) were measured in 44 infants/toddlers using the raised volume rapid thoracoabdominal compression method. SB-FENO was measured at 50 mL/s, and tidal-FENO was measured during awake tidal breathing. Clinical outcomes were assessed at age 3 years in 42 infants. Follow-up iPFTs were completed between ages 2.5-3 years in 32 subjects. RESULTS: An enrolment SB-FENO concentration ≥ 30 p.p.b. predicted persistence of wheezing at age 3 years with a sensitivity of 77%, a specificity of 94%, and an area under the curve (AUC) of 0.86 (95% CI: 0.74-0.98). The sensitivity, specificity, positive predictive, and negative predictive values of SB-FENO for persistence of wheezing and exacerbations were superior to tidal-FENO , BDR, and the API. SB-FENO ≥ 30 p.p.b. and tidal-FENO ≥ 7 p.p.b. measured at enrolment was associated with a decline in both FEV0.5 and FEF25-75 between enrolment and age 3 years. CONCLUSIONS: In wheezy infants/toddlers, SB-FENO was superior to tidal-FENO , BDR, and the API in predicting future exacerbations and persistence of wheezing at age 3 years. Both SB-FENO and tidal-FENO were associated with lung function decline over time.

Chronic wet cough: Protracted bronchitis, chronic suppurative lung disease and bronchiectasis.

The role of persistent and recurrent bacterial infection of the conducting airways (endobronchial infection) in the causation of chronic respiratory symptoms, particularly chronic wet cough, has received very little attention over recent decades other than in the context of cystic fibrosis (CF). This is probably related (at least in part) to the (a) reduction in non-CF bronchiectasis in affluent countries and, (b) intense focus on asthma. In addition failure to characterize endobronchial infections has led to under-recognition and lack of research. The following article describes our current perspective of inter-related endobronchial infections causing chronic wet cough; persistent bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis. In all three conditions, impaired muco-ciliary clearance seems to be the common risk factor that provides organisms the opportunity to colonize the lower airway. Respiratory infections in early childhood would appear to be the most common initiating event but other conditions (e.g., tracheobronchomalacia, neuromuscular disease) increases the risk of bacterial colonization. Clinically these conditions overlap and the eventual diagnosis is evident only with further investigations and long term follow up. However whether these conditions are different conditions or reflect severity as part of a spectrum is yet to be determined. Also misdiagnosis of asthma is common and the diagnostic process is further complicated by the fact that the co-existence of asthma is not uncommon. The principles of managing PBB, CSLD and bronchiectasis are the same. Further work is required to improve recognition, diagnosis and management of these causes of chronic wet cough in children.

Comparison of local risk factors for children's atopic symptoms in Hanoi, Vietnam.

BACKGROUND: A 1999 study in Hanoi, Vietnam using the International Study on Asthma and Allergies in Childhood (ISAAC) questionnaire showed a high prevalence of atopic symptoms. Identifying risk factors for symptoms in these children may help in understanding the causes for these high estimates. METHODS: An ISAAC questionnaire with supplemental questions on environmental variables was distributed to 5495 school children in Hanoi and a suburban district, Dong Anh. The response rate was 65.7%. RESULTS: In Dong Anh, the following were among the significant age and gender adjusted associations: pig ownership [odds ratio (OR) (95% confidence interval), OR = 1.79 (1.18-2.70) for doctor-diagnosed asthma (DDA), OR = 1.72 (1.08-2.78) for doctor diagnosed hay fever (DDHF)] and farming [OR = 1.67 (1.27-2.19) for ever asthma, OR = 1.51 (1.09-2.09) for DDHF]. In multivariate models, tuberculosis (TB) was a significant predictor of atopic symptoms [Hanoi: OR = 3.09 (1.10-8.70) for DDA, Dong Anh: OR = 3.71 (1.40-9.84) for DDA, OR = 4.66 (1.88-11.57) for DDHF]. CONCLUSIONS: These findings are contrary to the "hygiene hypothesis". Recent immunologic and epidemiologic studies refute the inverse association between allergy and TB and may be one explanation for the positive association in this study. The positive association with pig ownership and farming may be because of exposures on farms in a developing country that may be different from exposures in farms of developed countries.

Differences in asthma prevalence between samples of American Indian and Alaska Native children.

OBJECTIVES: To better understand the prevalence of asthma among American Indian and Alaska Native (AI/AN) children and to explore the contribution of locale to asthma symptoms and diagnostic assignment, the authors surveyed AI/AN middle school students, comparing responses from metropolitan Tacoma, Washington (metro WA) and a non-metropolitan area of Alaska (non-metro AK). METHODS: Students in grades 6-9 completed an asthma screening survey. The authors compared self-reported rates of asthma symptoms, asthma diagnoses, and health care utilization for 147 children ages 11-16 self-reporting as AI/AN in metro WA and 365 in non-metro AK. RESULTS: The prevalences of self-reported asthma symptoms were similar for the metro WA and non-metro AK populations, but a significantly higher percentage of metro WA than of non-metro AK respondents reported having received a physician diagnosis of asthma (OR 2.33; 95% CI 1.23, 4.39). The percentages of respondents who reported having visited a medical provider for asthma-like symptoms in the previous year did not differ. CONCLUSIONS: The difference in rates of asthma diagnosis despite similar rates of asthma symptoms and respiratory-related medical visits may reflect differences in respiratory disease patterns, diagnostic labeling practices, or environmental factors. Future attempts to describe asthma prevalence should consider the potential contribution of non-biologic factors such as diagnostic practices.

Current concepts in adult respiratory distress syndrome in children.

Acute respiratory distress syndrome (ARDS) is an acute form of severe alveolar-capillary injury that evolves after a direct or indirect lung insult. It begins as noncardiogenic pulmonary edema and develops into a neutrophilic alveolitis, and, later, pulmonary fibrosis. Mortality remains high among children with ARDS, particularly when serious underlying conditions co-exist, sepsis occurs, and when there is multi-organ failure. Lung function improves with time among survivors, but pulmonary fibrosis may persist. Advances in the care of children with ARDS include the use of lung-protective ventilator strategies, permissive hypercapnia, inhaled nitric oxide, high-frequency ventilation, and extra-corporeal life support. These approaches reduce ventilator-associated lung injury and may improve survival when used in combination with one another. Interventions that reduce alveolar inflammation, enhance alveolar fluid removal, and reduce pulmonary fibrosis will further improve survival and recovery from ARDS in the future.

Practice of pediatric pulmonology: results of the Future of Pediatric Education Project (FOPE)

In 1996, the Future of Pediatric Education (FOPE) Project of the American Academy of Pediatrics (AAP) developed surveys to describe the nature of pediatric practices, recent trends in clinical practice, and anticipated workforce needs for both pediatric generalists and pediatric sub-specialists. A survey was specifically developed to describe the features of pediatric pulmonology as self-reported by pediatric pulmonologists. The survey was distributed to members of the AAP Pulmonology Section, the Pediatric Assembly of the American Thoracic Society, and certified pediatric pulmonologists recognized by the American Board of Pediatrics. Of the 535 respondents (67% of those invited to respond), the responses of 388 certified and 94 trained but not board-certified pulmonologists were included in the results. The characteristics of certified and non-certified respondents were the same for most survey questions. Clinical activities occupy 73 +/- 29% of professional time. Most pulmonologists work in urban, inner city, or suburban settings and 85% are affiliated with a medical school. One third are in private practice. As a group, research activities occupy less than 15% of their time. Most pediatric pulmonologists maintain a referral practice and use physician extenders to provide care. Patients with asthma and cystic fibrosis comprise 60-70% of patient volume. Both the volume and complexity of patients are increasing, as is competition for pediatric sub-specialty services. Pediatric pulmonary practices vary in size and in volume of patients that they manage in various settings. Forty percent of respondents identify allergists and other pediatric pulmonologists as sources of competition. Sixty-nine percent of respondents do not believe that there is a current need for additional pediatric pulmonologists in their respective communities. Only 15% of respondents plan to retire in the next decade.

Impact of respiratory syncytial virus immune globulin in 1996-1997: a local controlled comparison.

BACKGROUND: Immune globulin containing high titers of neutralizing antibodies specific for respiratory syncytial virus (RSV) is clinically used to prevent hospitalizations for RSV-related respiratory infections among high-risk infants. However, recommendations regarding which patient populations should receive RSV immune globulin are inconsistent. OBJECTIVE: To compare hospitalization rates for prematurely born infants with and without chronic lung disease who received RSV immune globulin with similar infants whose parents refused such treatment during the 1996-1997 winter season. DESIGN: Inception cohort study. PARTICIPANTS: Infants born at less than 35 weeks' gestation and less than 6 months old without lung disease and children who had been born prematurely, had chronic respiratory disease, and were less than 2 years old at the onset of the RSV season. MAIN OUTCOME MEASURE: Hospitalization for an RSV-related respiratory illness. RESULTS: Seventy-six infants (66 [87%] with chronic lung disease and 10 [13%] born prematurely without lung disease) received RSV immune globulin; 65 infants (18 [28%] with chronic lung disease and 47 [72%] born prematurely without lung disease) did not. Three (4%) of the treated group and 2 (3%) of the untreated group were hospitalized for RSV infections. Of those with chronic lung disease, 5% (3/66) of those treated with RSV immune globulin were hospitalized, compared with 11% (2/18) of those untreated. Of those born prematurely without lung disease, no infant in the treated (0/10) or untreated (0/47) group was hospitalized. CONCLUSIONS: The risk of hospitalization of infants born prematurely who are younger than 6 months without lung disease is low. Current recommendations for preventing RSV illness in this group by using RSV immune globulin may require inclusion of more specific clinical characteristics rather than gestational age alone.

The impact of asthma and asthma-like illness in Seattle school children.

The impact of asthma and asthma-like illness was measured in a population of 5-9-year-old Seattle public school children. Child health information was obtained from a survey of 1665 parents of first and second grade students to assess medical services use and impaired physical functioning among diagnosed asthmatics and those with current wheezing, defined as wheezing in the past 12 months without a diagnosis of asthma, relative to an asymptomatic population with neither condition. Relative to the asymptomatic population, the prevalence of respiratory-related activity limitation, and perception of poorer child health was larger among diagnosed asthmatics than children with current wheezing. However, the prevalence of sleep disturbances, school absences, medical services use, and parental concern over their child's health was similar for both the asthmatic and wheezing groups relative to the asymptomatic group. Also, in both symptomatic groups, a history of moderate or severe wheezing was associated with an increased prevalence of respiratory-related sleep disturbances and activity limitation. The similarity between the impact of diagnosed asthma and undiagnosed asthma-like illness suggests that the overall social and economic burden of asthma may be higher than previously estimated.

The Asthma Outreach Project: a promising approach to comprehensive asthma management.

We describe a pilot system of coordinated asthma care emphasizing home visits by a community-based lay worker collaborating with a pediatrician, pharmacist, and public health nurse. Study participants included 23 low-income children with moderate to severe asthma and their families at an inner-city pediatric clinic. This system was successfully implemented, and client satisfaction was extremely high. Utilization review showed a reduction in hospitalizations, emergency department visits, and unscheduled clinic visits, and an increase in follow-up clinic visits. This model of care may reduce unscheduled service use and deserves further study as an alternative for asthma management among similar patient populations.

Randomized, multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe, persistent pulmonary hypertension of the newborn.

BACKGROUND: Although inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in newborn infants with persistent pulmonary hypertension, its effects are variable. We hypothesized (1) that the response to iNO therapy is dependent on the primary disease associated with persistent pulmonary hypertension of the newborn (PPHN) and (2) that the combination of high-frequency oscillatory ventilation (HFOV) with iNO would be efficacious in patients for whom either therapy alone had failed. METHODS: To determine the relative roles of iNO and HFOV in the treatment of severe PPHN, we enrolled 205 neonates in a randomized, multicenter clinical trial. Patients were stratified by predominant disease category: respiratory distress syndrome (n = 70), meconium aspiration syndrome (n = 58), idiopathic PPHN or pulmonary hypoplasia (excluding congenital diaphragmatic hernia) ("other": n = 43), and congenital diaphragmatic hernia (n = 34); they were then randomly assigned to treatment with iNO and conventional ventilation or to HFOV without iNO. Treatment failure (partial pressure of arterial oxygen [PaO2] < 60 mm Hg) resulted in crossover to the alternative treatment; treatment failure after crossover led to combination treatment with HFOV plus iNO. Treatment response with the assigned therapy was defined as sustained PaO2 of 60 mm Hg or greater. RESULTS: Baseline oxygenation index and PaO2 were 48 +/- 2 and 41 +/- 1 mm Hg, respectively, during treatment with conventional ventilation. Ninety-eight patients were randomly assigned to initial treatment with HFOV, and 107 patients to iNO. Fifty-three patients (26%) recovered with the initially assigned therapy without crossover (30 with iNO [28%] and 23 with HFOV [23%]; p = 0.33). Within this group, survival was 100% and there were no differences in days of mechanical ventilation, air leak, or supplemental oxygen requirement at 28 days. Of patients whose initial treatment failed, crossover treatment with the alternate therapy was successful in 21% and 14% for iNO and HFOV, respectively (p = not significant). Of 125 patients in whom both treatment strategies failed, 32% responded to combination treatment with HFOV plus iNO. Overall, 123 patients (60%) responded to either treatment alone or combination therapy. By disease category, response rates for HFOV plus iNO in the group with respiratory syndrome and the group with meconium aspiration syndrome were better than for HFOV alone or iNO with conventional ventilation (p < 0.05). Marked differences in outcomes were noted among centers (percent death or treatment with extracorporeal membrane oxygenation = 29% to 75%). CONCLUSIONS: We conclude that treatment with HFOV plus iNO is often more successful than treatment with HFOV or iNO alone in severe PPHN. Differences in responses are partly related to the specific disease associated with PPHN.

Passive smoke exposure impairs recovery after hospitalization for acute asthma.

OBJECTIVE: To determine if children with chronic asthma hospitalized for an acute exacerbation experienced prolonged clinical recovery after hospital discharge if they returned to a home environment in which they were exposed to environmental tobacco smoke. DESIGN: A prospective longitudinal study. SETTING: Children's Hospital and Medical Center, Seattle, Wash. PATIENTS: Patients admitted to the emergency department of the Children's Hospital and Medical Center with the single diagnosis of asthma (International Classification of Diseases, Ninth Revision [ICD-9] code 493). RESULTS: Twenty-two children with acute asthma were sequentially enrolled in the study and longitudinally observed between February and -June 1994. The tobacco-smoking group (n = 11) was defined as having at least 1 smoker in the home. The nonsmoking group (n = 11) had no environmental tobacco smoke exposure at home. The 2 groups were similar in age, sex, preadmission chronic asthma severity, and immediate predischarge asthma status. Discharge medication use was similar in the 2 groups During a 1 month follow-up period, the tobacco-smoking group had a significantly greater number of symptomatic days than the nonsmoking group (P < .05) Of the children in the nonsmoking group, 9 (82%) had less than 1 symptomatic day per week compared with 3 (27%) in the tobacco-smoking group. beta 2-Agonist bronchodilator use declined significantly (P < .001) during follow-up in the nonsmoking group but not in the tobacco-smoking group, despite similar anti-inflammatory drug therapy in both groups. CONCLUSIONS: Recovery by children after hospitalization for acute asthma is impaired by environmental tobacco smoke exposure when the period of recovery is characterized by persistent respiratory symptoms and use of asthma medication for symptomatic relief. These findings underscore the need to limit environmental tobacco smoke exposure in children with asthma and argue for closer physician follow-up of those children returning to a home environment in which smokers are present.

Indoor risk factors for asthma and wheezing among Seattle school children.

Indoor risk factors for physician-diagnosed asthma and wheezing in the past 12 months without previous asthma diagnosis were assessed in a survey of parents of 5-9-year-old Seattle primary school students. Among the 925 respondents, 106 (11%) reported a physician diagnosis of asthma, 66 (7%) had wheezing without diagnosis, and 753 (82%) were asymptomatic. After adjusting for age, sex, gender, ethnicity, medical history, socioeconomic status (SES) and parental asthma status, an increased risk of physician diagnosis of asthma was associated with household water damage, the presence of one or more household tobacco smokers, and at least occasional environmental tobacco smoke (ETS) exposure. Similarly, an increased risk of wheezing in the past 12 months among children without diagnosed asthma was associated with household water damage, presence of one or more household tobacco smokers, and occasional or more frequent ETS exposure. No increased risk of either condition was associated with gas, wood, or kerosene stove use, household mold, basement water, or wall/window dampness. Similarities in the indoor risk factors patterns between diagnosed asthma and wheezing without diagnosis suggested a similar etiology of these two conditions. The slightly higher association between ETS and asthma may indicate that parents of diagnosed asthmatics were more conscious of ETS, and were more likely to prohibit household smoking by resident smokers. Future research is needed to quantify which aspects of household water damage are related to respiratory illness.

Lung hyaluronan decreases during group B streptococcal pneumonia in neonatal piglets.

Neonatal Group B streptococcus (GBS) sepsis and pneumonia result in lung injury and remain a major cause of morbidity and mortality in the newborn. Increased lung hyaluronan (HA) content is an important component of the lung's early response to damage in diseases such as adult respiratory distress syndrome (ARDS), infant respiratory distress syndrome (IRDS), and bleomycin-induced fibrosis. It is known, however, that GBS virulence factors include specific secretory enzymes such as hyaluronidase, an enzyme which breaks down HA. We therefore hypothesized that in lobar GBS pneumonia, lung HA would be decreased compared with normal values, and that in lobar pneumonia with atelectasis, lung HA would be further decreased because of increased substrate availability. The right lower lobes (RLL) and left lower lobes (LLL) of anesthetized piglets 16 +/- 2 d old were each selectively inoculated with 1 x 10(9) colony-forming units (CFU) GBS via an endobronchial catheter (n = 7). The LLL was subsequently collapsed by endobronchial occlusion following 10 min of 100% O2. Control animals (n = 6) was anesthetized, instrumented, and ventilated without exposure to GBS. At 4 h, lungs were removed and HA extracted and assayed using a competitive inhibition assay. HA extracted from areas of lobar pneumonia was significantly decreased (27 +/- 6.6 micrograms/g wet lung, p < 0.005) when compared with control values of control piglets (51 +/- 19.6 micrograms/g wet lung). Atelectasis plus lobar pneumonia further decreased lung HA to 10 +/- 13.3 micrograms/g wet lung, p < 0.0001. We conclude that lobar GBS decreases lung HA and that this process is augmented by collapsed lung regions, and speculate that this departure from the usual early lung response to injury contributes to GBS invasion of lung parenchyma.

Effect of nitric oxide synthase inhibition during group B streptococcal sepsis in neonatal piglets.

Nitric oxide (NO), an important vasodilatory modulator of systemic and pulmonary vascular tone, is synthesized from L-arginine by the enzyme NO synthase in vascular endothelial and smooth muscle cells. L-Arginine analogs, such as N omega-nitro-L-arginine methyl ester (L-NAME), are competitive antagonists of NO synthase and inhibit NO synthesis. Group B streptococcus (GBS) causes pulmonary hypertension, hypoxemia, lung vascular injury, and reduced cardiac output in both human newborns and neonatal piglets. Lung vascular injury associated with prolonged GBS infusion in piglets may attenuate NO production and thus promote severe pulmonary hypertension. We studied the effect of the NOS inhibitor, L-NAME and the precursor of NO, L-arginine, on pulmonary and systemic hemodynamics during late-phase GBS sepsis in the piglet model. Neonatal piglets were anesthetized, ventilated with room air, and randomized to receive a continuous infusion of saline (n = 5) or GBS (n = 5) for 4 h. After 3 h of infusion, both groups received a bolus of L-NAME (3 mg/kg). Hemodynamic and gas exchange indices were measured at baseline, 30 min, and 3 h of infusion, and 30 min and 1 h after L-NAME treatment. L-NAME treatment caused 1) significant increases in mean pulmonary arterial pressure, pulmonary vascular resistance, mean systemic arterial pressure, and systemic vascular resistance for both groups; 2) a similar percentage of increase in pulmonary vascular resistance for the two groups; 3) greater reduction in cardiac output and SV in the GBS compared with the control group; and 4) no significant alterations in arterial partial pressure of oxygen or the difference between alveolar and arterial partial pressure of oxygen for either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of amrinone during group B Streptococcus-induced pulmonary hypertension in piglets.

Intravenous infusion of group B Streptococcus (GBS) into neonatal animals produces pulmonary hypertension, ventilation/perfusion (VA/Q) mismatch, and an increase in serum levels of thromboxane B2 (TxB2) and tumor necrosis factor (TNF) alpha. The vasodilator amrinone (amr) is a cGMP-inhibited phosphodiesterase inhibitor and is reported to inhibit thromboxane A2 and TNF production. We hypothesized that infusion of amr would cause pulmonary vasodilation and reduce serum TxB2 and TNF levels in piglets with late phase GBS-induced pulmonary hypertension. The effect of amr on gas exchange was also determined. A continuous infusion of GBS was administered for 5 hr to 4 groups of anesthetized, mechanically ventilated neonatal piglets. An amr bolus of 8 mg/kg was given at 4 hr followed by a 1 hr continuous infusion of either 10 or 20 micrograms/kg/min of amr (amr 10 and amr 20, respectively). Control piglets received a bolus and 1 hr infusion of amr carrier. The infusion of amr, but not of carrier reversed late phase GBS-induced pulmonary hypertension. Piglets infused with amr 20 showed transient selective pulmonary vasodilation, based on a reduced ratio of pulmonary to systemic vascular resistance (PVR/SVR ratio) value at 30 min but not at 1 hr, compared to pre-amr treatment values. The PVR/SVR ratio values for amr 10 and control group did not change after treatment with either amr or carrier. Treatment with amr 10 or 20 did not decrease serum TxB2 or TNF levels or increase VA/Q mismatch.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of inhaled nitric oxide during group B streptococcal sepsis in piglets.

Group B streptococcus (GBS), a common gram-positive pathogen, causes similar pathophysiologic changes in newborn humans and animals. Infusion of GBS into neonatal animals produces pulmonary hypertension and ventilation/perfusion (Va/Q) mismatch in both early-phase (< 1 h) and late-phase (2 to 6 h) responses. Contrary to early phase, late phase causes pulmonary vascular injury. Nitric oxide (NO) is an inhaled vasodilator whose effect on pulmonary hypertension and Va/Q matching during early and late phases of GBS sepsis is unclear. We hypothesized that inhaled NO (150 ppm) would: (1) reverse early-phase GBS-induced pulmonary hypertension; (2) demonstrate less effectiveness in reversing late-phase GBS-induced pulmonary hypertension because of vascular injury; (3) improve late-phase GBS-induced Va/Q mismatching. Anesthetized, mechanically ventilated piglets (n = 10; 14 +/- 4 days of age) received a 240-min infusion of GBS (1.5 x 10(9) CFU/kg/h). Piglets received 30 min of NO (Study) or N2 (Control) at 30 and 210 min of GBS infusion. We found that inhaled NO selectively reversed early- and late-phase GBS-induced pulmonary hypertension and that NO was equally as effective in each phase. Inhaled NO did not reverse Va/Q mismatching during late-phase GBS. We conclude that 4 h of GBS sepsis does not injure neonatal pulmonary vascular smooth muscle sufficiently to impair its response to inhaled NO.

Lung vascular responses and VA/Q matching after chronic hypoxia in neonatal piglets.

We hypothesized that exposure of neonatal swine to chronic alveolar hypoxia (CH) would cause increased PVR, blunt acute hypoxic vasoconstriction, and increase VA/Q mismatch. After exposure to either normobaric alveolar hypoxia (FIO2 = 0.10) or room air for 2 weeks, animals were anesthetized and ventilated first with room air and then with hypoxic gas (FIO2 = 0.12). PVR, and pressure-flow (P/Q) relations were measured between 15-100% of baseline cardiac output. VA/Q matching was measured by the multiple inert gas elimination technique. During room air breathing, the mean PVR and P/Q slope in the CH animals was significantly greater than in the control (C) animals. P/Q intercepts were similar and near the origin for both groups. The absolute PVR and P/Q slope were greater for CH compared to C animals during acute alveolar hypoxia. The fractional increase in PVR and P/Q slope in the response to acute hypoxia was similar for both groups. PaO2, intrapulmonary shunt, and SDQp (an index of VA/Q heterogeneity) were similar for both groups. We conclude that CH in neonatal swine causes pulmonary hypertension, but does not attenuate acute hypoxic pulmonary vasoconstriction, nor VA/Q matching.