Transcutaneous oxygen tension measurements during graded hemorrhage and reinfusion

Measurement of transcutaneous oxygen tension (PtCO2) has been suggested as a useful monitoring tool in the hypovolemic patient. Our study was undertaken to evaluate changes in PtCO2 that occur during graded hemorrhage and reinfusion, and to compare PtCO2 values to standard cardiorespiratory and biochemical parameters during hypovolemia. Seven mongrel dogs were bled 50% of their estimated blood volume (44 mL/kg) over one hour. This was followed by a one-hour monitoring period, a 30-minute reinfusion period, and an additional one-hour monitoring period. Pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), cardiac output (CO), mean arterial pressure (MAP), mixed venous oxygen tension (MvO2), arterial blood gases, and PtCO2 were measured serially throughout the study period. Cardiac index (CI), peripheral vascular resistance (PVR), O2 consumption, delivery, and percentage of extraction were calculated for each sampling period. A statistically significant fall in CI, MvO2 and PCWP occurred following the first 10% of blood loss; PtCO2 and MAP fell significantly after 20% hemorrhage; CVP fell after 30% hemorrhage. PtCO2 rose significantly after the first 10% of reinfusion, and it continued to rise during the entire reinfusion period, as did MvO2, CO, MAP, CVP, and PCWP. In contrast to the other measured variables, the elevations in PtCO2, and MvO2 were more pronounced early in the reinfusion period. During postreinfusion monitoring, PtCO2, MvO2, CO, and PCWP fell significantly despite maintenance of prehemorrhage MAP and CVP. Overall PtCO2 correlated well with MvO2 and the O2 extraction ratio, and to a lesser extent with CI, MAP, and O2 delivery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Aging on the Relationship between Asthma Severity and Bronchial Hyperresponsiveness in Children with Asthma

An association between asthma and bronchial hyperresponsiveness (BHR) has been demonstrated. It is possible that the relationship between asthma severity and BHR in children with asthma is different in infants and in adolescents. The aim of this study is therefore to evaluate the effect of aging on the relationship between the severity of asthma and BHR in children with asthma.

We measured BHR in 386 subjects ranging from 2 to 20 years of age. The subjects consisted of 323 children with asthma (boys : girls = 193 : 130, mean age 9.7 years) and 63 age-matched controls (boys : girls = 25 : 38, mean age 8.2 years). BHR was measured using the methacholine inhalation challenge by measuring the transcutaneous oxygen pressure (tcPO₂) in children less than 6 years of age (Dmin-PO₂) and by measuring the respiratory resistance (Rrs) in children 6 years of age and older (Dmin-Rrs). Throughout the whole age range, both the Dmin-PO₂ and Dmin-Rrs in each asthma severity group were higher than those in the controls. In the asthmatics aged 2–5 years, the Dmin-PO₂ levels in the mild asthma group were higher than those in the moderate and severe asthma groups (p < 0.001, p < 0.001, respectively), and the Dmin-PO₂ levels in the moderate asthma group were also higher than those in the severe asthma group. This tendency was also found in the age ranges of 6–9 years and 10–13 years. In the asthmatics aged 14–20 years, the Dmin-Rrs levels were not significantly different among the three groups.

Taken together, these data show that aging has an effect on the relationship between the severity of asthma and BHR during childhood and that BHR may not be the sole determinant for the severity of asthma in adolescence.     

Relationship between bronchial hyperresponsiveness and development of asthma in children with chronic cough

To evaluate the relationship between bronchial hyperresponsiveness (BHR) and the development of asthma in children with chronic cough, we performed methacholine inhalation challenges and transcutaneous oxygen pressure (tcPO2) measurements in 92 children with chronic cough aged from 1-13 years (55 boys and 37 girls; mean, 5.3 years) and followed them for > or = 10 years. Forty-four age-matched children with asthma (24 males and 20 females; mean, 6.5 years) and 44 age-matched children without cough or asthma served as controls (18 males and 26 females; mean, 4.6 years). Consecutive doubling doses of methacholine were inhaled until a 10% decrease in tcPO2 from baseline was observed. The cumulative dose of methacholine at the inflection point of the tcPO2 record (Dmin-PO2) was considered to represent hyperresponsiveness to inhaled methacholine. After 10 years or more of follow-up, 60 of the 92 subjects with cough answered our questionnaire, and 27/60 had been diagnosed with asthma. There was a statistical difference in Dmin-PO2 between the children who presented with chronic cough originally and who developed asthma (asthma-developed group) and those who did not develop asthma (asthma-free group). There was no difference in the value of Dmin-PO2 between the asthma-developed group and the asthma group, or between the asthma-free group and the age-matched control group. Among the children with chronic cough, there was no difference in Dmin-PO2 between girls and boys, either in the asthma-developed group or in the asthma-group. We conclude that 45% of the children with a chronic cough in early life developed asthma, and that BHR in children with chronic cough during the childhood period is a strong risk factor for the development of asthma.     

Determinants of bronchial responsiveness to methacholine at school age in twin pairs

The methacholine inhalation challenge test (MIC) was used to evaluate bronchial responsiveness in 67 children who were the products of multiple pregnancies when they were 7-15 years old. At birth, 30 (45%) infants had intrauterine growth retardation (IUGR; birth weight <2 SD below normal birth weight, or birth weight difference >1.3 SD between twin-pairs), and 59 (88%) were born before 37 weeks of gestation. None of the children had doctor-diagnosed asthma. The provocative dose of methacholine causing a 20% fall in Wright's peak expiratory flow (WPEF) (PD20) was below 1,000 microg in 10 (15%) children, and they were classified as MIC responders. There were no differences in perinatal or neonatal factors between MIC responders and nonresponders; in particular, MIC responses did not differ between IUGR infants, and children with appropriate growth for gestational age (AGA) at birth. There were seven discordant pairs in which one child was a MIC responder and the other was not; 5 responders were IUGR, and 2 were AGA children (ns). Respiratory tract infections after the neonatal period were equally common in IUGR and AGA children. However, these infections were associated with later bronchial hyperresponsiveness. Doctor-diagnosed respiratory infections, numbers of antibiotic courses, episodes of otitis media, and the need for adenoidectomy, tonsillectomy, and tympanostomy were more common in MIC responders than in nonresponders. We conclude that IUGR was not associated with subsequent bronchial hyperresponsiveness in twin pairs assessed by the MIC test. A significant relationship was seen between bronchial hyperresponsiveness and infections after the neonatal period.     

Effect of Age on Bronchial Reactivity in Children with Asthma

In contrast to an abundance of data concerning age-related changes of bronchial sensitivity, the relationship between age and rapidity of bronchoconstriction (bronchial reactivity) remains unclear. We studied age and bronchial reactivity in children with asthma. Enrolled in this study were 511 asthmatic subjects and 115 age-matched control subjects 1 to 16 years of age. Bronchial reactivity was represented by the slope of the methacholine transcutaneous oxygen pressure dose-response curve (SPO₂) in younger children and the slope of the respiratory resistance dose-response curve (SRrs) in older children. Overall, SPO₂ and SRrs were higher in asthmatic than control subjects. SPO₂ increased significantly from 1 to 6 years in asthmatic subjects, reaching a plateau after age 7. This age-related change in SPO₂ also was seen in controls. SRrs in asthmatic subjects decreased after age 13, while SRrs in controls showed no significant change between age 7 and 16. Age-related change in bronchial reactivity occurs during childhood, possibly reflecting early changes in airway smooth muscle maturity and later changes in airway wall rigidity.     

Effect of Age on Bronchial Reactivity in Children with Asthma

In contrast to an abundance of data concerning age-related changes of bronchial sensitivity, the relationship between age and rapidity of bronchoconstriction (bronchial reactivity) remains unclear. We studied age and bronchial reactivity in children with asthma. Enrolled in this study were 511 asthmatic subjects and 115 age-matched control subjects 1 to 16 years of age. Bronchial reactivity was represented by the slope of the methacholine transcutaneous oxygen pressure dose-response curve (SPO₂) in younger children and the slope of the respiratory resistance dose-response curve (SRrs) in older children. Overall, SPO₂ and SRrs were higher in asthmatic than control subjects. SPO₂ increased significantly from 1 to 6 years in asthmatic subjects, reaching a plateau after age 7. This age-related change in SPO₂ also was seen in controls. SRrs in asthmatic subjects decreased after age 13, while SRrs in controls showed no significant change between age 7 and 16. Age-related change in bronchial reactivity occurs during childhood, possibly reflecting early changes in airway smooth muscle maturity and later changes in airway wall rigidity.     

Airway hyperreactivity detected by methacholine challenge in children with sickle cell disease

Recent studies have emphasized the presence of airway hyperreactivity (AHR) in children with sickle cell disease (SCD). However, various tests for the detection of AHR have yielded distinctly different results in these patients. This study identified AHR via a methacholine challenge test (MCT) in a group of children with SCD (31 patients; age range, 6-16 years). The results of pulmonary function tests (PFTs) in patients with SCD and age-matched controls (30 healthy children) were investigated and compared. A positive methacholine challenge result was noted in 25 patients (77.5%). We found that when compared with controls, the children with SCD had lower forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV(1)) and that both their forced expiratory flow at 25-75% of the FVC (FEF(25-75)) and their FEV(1)/FVC ratio were not statistically significantly different from those of the controls. The statistically significant differences remained after treatment with a bronchodilator agent, but the changes in the FVC, FEV(1), and FEF(25-75) in response to bronchodilator treatment did not differ with statistical significance between the two groups. There was a negative correlation between the number of ACS attacks and the percent predicted of the FEV(1) and the FEV(1)/FVC ratio. We found that the MCT reveals a high incidence of AHR in patients with SCD, regardless of whether those individuals have ACS.     

Evaluation of interrupter resistance in methacholine challenge testing in children

Bronchial hyperresponsiveness (BHR) is a key feature of asthma and is assessed using bronchial provocation tests. The primary outcome in such tests (a 20% decrease in forced expiratory volume in 1 sec (FEV₁)) is difficult to measure in young patients. This study evaluated the sensitivity and specificity of the interrupter resistance (R_int) technique, which does not require active patient participation, by comparing it to the primary outcome measure. Methacholine challenge tests were performed in children with a history of moderate asthma and BHR. Mean and individual changes in R_int and FEV₁ were studied. A receiver operating characteristic (ROC) curve was used to describe sensitivity and specificity of R_int. Seventy‐three children (median age: 9.2 years; range: 6.3–13.4 years) participated. There was a significant (P < 0.01) increase in mean R_int with increasing methacholine doses. However, individual changes of R_int showed large fluctuations. There was great overlap in change of R_int between children who did and did not reach the FEV₁ endpoint. A ROC curve showed an area under the curve of 0.65. Because of low sensitivity and specificity, the use of R_int to diagnose BHR in individual patients seems limited. Pediatr Pulmonol. 2011; 46:266–271. © 2011 Wiley‐Liss, Inc.     

Changes in the highest frequency of breath sounds without wheezing during methacholine inhalation challenge in children

A breath sound analyser was used to detect bronchoconstriction without wheezing during methacholine inhalation challenge in children. The highest frequency of inspiratory breath sounds increased significantly during bronchoconstriction and decreased after inhalation of a bronchodilator. The highest frequency of inspiratory breaths sounds was correlated with bronchial reactivity. Background and objective: It is difficult for clinicians to identify changes in breath sounds caused by bronchoconstriction when wheezing is not audible. A breath sound analyser can identify changes in the frequency of breath sounds caused by bronchoconstriction. The present study aimed to identify the changes in the frequency of breath sounds during bronchoconstriction and bronchodilatation using a breath sound analyser. Methods: Thirty‐six children (8.2 ± 3.7 years; males : females, 22 : 14) underwent spirometry, methacholine inhalation challenge and breath sound analysis. Methacholine inhalation challenge was performed and baseline respiratory resistance, minimum dose of methacholine (bronchial sensitivity) and speed of bronchoconstriction in response to methacholine (Sm: bronchial reactivity) were calculated. The highest frequency of inspiratory breath sounds (HFI), the highest frequency of expiratory breath sounds (HFE) and the percentage change in HFI and HFE were determined. The HFI and HFE were compared before methacholine inhalation (pre‐HFI and pre‐HFE), when respiratory resistance reached double the baseline value (max HFI and max HFE), and after bronchodilator inhalation (post‐HFI and post‐HFE). Results: Breath sounds increased during methacholine‐induced bronchoconstriction. Max HFI was significantly greater than pre‐HFI (P < 0.001), and decreased to the basal level after bronchodilator inhalation. Post‐HFI was significantly lower than max HFI (P < 0.001). HFI and HFE were also significantly changed (P < 0.001). The percentage change in HFI showed a significant correlation with the speed of bronchoconstriction in response to methacholine (P = 0.007). Conclusions: Methacholine‐induced bronchoconstriction significantly increased HFI, and the increase in HFI was correlated with bronchial reactivity.     

Hospital admission for acute painful episode following methacholine challenge in an adolescent with sickle cell disease

Asthma is associated with increases in sickle cell disease (SCD)‐related morbidity and mortality. A thorough evaluation for asthma in children with SCD is important and may involve methacholine challenge (MCh). In this report, we present a 14‐year‐old male with SCD who was admitted for an acute painful episode following MCh. Pain events after MCh have not been previously reported in children with SCD. The risk–benefit ratio should be strongly considered prior to performance of MCh in this patient population, and all possible complications, including an acute painful episode, should be openly discussed with the parents and pediatric patient. Pediatr Pulmonol. 2009; 44:728–730. © 2009 Wiley‐Liss, Inc.     

Measurement of bronchial responsiveness in young children: comparison of transcutaneous oxygen tension and functional residual capacity during induced bronchoconstriction and -dilatation.

Demonstration of an increased bronchial responsiveness in preschool children may support the diagnosis of asthma. Most young children cannot perform routine lung function tests. Transcutaneous PO2 (PtcO2) measurement has been applied successfully in young children, and changes in PtcO2 have been shown to correlate well with changes in forced expiratory volume in 1 second (FEV1) during bronchoprovocation testing with methacholine. PtcO2 is, however, an indirect measure of the effect of inhaled spasmogens. As functional residual capacity (FRC) can also be measured by helium dilution spirometry in preschool children, we compared PtcO2 and FRC during methacholine inhalation challenges and after inhaled terbutaline, in order to determine whether FRC is useful as a more direct measure of induced bronchoconstriction and -dilatation than PtcO2. We studied 41 allergic asthmatic children (mean age, 5.2 years) who underwent a methacholine bronchoprovocation test; 38 children received terbutaline 1 h after the final methacholine dose. The provocative concentration of methacholine that caused a 20% decrease of PtcO2 was determined, and changes in FRC and PtcO2 after each methacholine dose step were compared. Similarly, changes in PtcO2 and FRC before, and 15 and 30 min after, terbutaline were compared. All children had a drop in PtcO2 after increasing doses of methacholine; a 20% change was reached in 38 patients. Mean FRC values increased significantly but variably with increasing doses of methacholine, and changes in PtcO2 and FRC did not correlate. After terbutaline, PtcO2 increased slightly but significantly, and FRC again varied unpredictably. In a separate group of 11 children, the effect of terbutaline was assessed directly after the final methacholine dose, when significant bronchoconstriction was still present.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiorespiratory status in long-term survivors of prematurity, with and without hyaline membrane disease

Forty-eight children, born at less than 33 weeks' gestation and without bronchopulmonary dysplasia (BPD) or Wilson-Mikity syndrome (WM) were studied at a mean age of 9.1 years, to identify the incidence and possible factors contributing to the development of long-term abnormalities in pulmonary function. As neonates, 30 children had hyaline membrane disease (HMD) of whom 21 required ventilation. Eighteen did not have HMD, of whom 9 required ventilation for nonrespiratory reasons. All patients had grown normally. Four of the 48 (8.3%) had clinical asthma, 5 had persisting chest x-ray abnormalities (10.6% of 47 chest x-rays performed), each having been ventilated for HMD. There was a close association between duration of ventilation, oxygen administration, and subsequent abnormal chest x-ray. Electrocardiogram and M-mode echocardiograms were normal in all but 2 patients. Only 3 patients had significant restrictive lung disease, 3 had evidence of significant airways obstruction, and 13 (27.7%) had signs of air trapping. Methacholine challenge was positive in 30 of 46 patients (65.2%). The incidence of a positive methacholine challenge did not correlate with history of HMD, duration of ventilation, or high oxygen administration. There is an increased incidence of airway hyperreactivity in survivors of prematurity, not associated with any identified therapeutic maneuver during the neonatal period.     

Acinar arterial changes with chronic lung disease of prematurity in the surfactant era

Because echocardiographic studies on infants with chronic lung disease (CLD) suggest that pulmonary hypertension (PH) may contribute to its severity, we studied acinar arterial walls in the following surfactant-era infants: controls (n=38): 22-41 weeks of gestational age (GA), exposed briefly to oxygen and positive pressure ventilation, died within 48 hr of birth; prolonged rupture of fetal membranes (PROM) and persistent pulmonary hypertension (PPHN) (n=17); and SCORE (integrated area under curve of average daily FiO2 x average daily MAP) groups (<20, 20-69, and 70-500; mild, moderate, and severe clinical lung disease, respectively, n=35): 23-30 weeks GA, lived 7-79 days. Lungs were stained for elastic tissue and smooth muscle actin. Vessels were assessed for percent of vessel circumference with smooth muscle, extent of elastic laminae in the walls, and percent arterial wall thickness (%AWT) at three levels: terminal to respiratory bronchiole transition (TRB), alveolar duct, and saccule. At the alveolar ductal and saccular levels, percent arterial wall thickness (%AWT) in mild CLD (SCORE < 20) was less than controls (P < 0.05) and those with more severe CLD (SCORE 70-500), indicating that normal postnatal arterial wall thinning may be delayed, or there is remodeling associated with increased %AWT. Severe CLD infants also had a significantly higher percent of circumferential actin than those with milder disease (SCORE < or = 69) and controls. In moderate and severe CLD, there was an increase in extent of the elastic laminae compared to controls and mild CLD. These changes were also significantly greater in PROM and PPHN infants compared to even severe CLD. We conclude that PH is a real possibility in severe CLD infants after discharge at 36 weeks. Grading the severity of CLD at discharge, and echocardiographic studies, may guide subsequent oxygen therapy.     

家庭氧疗对COPD患者肺功能影响研究

目的 探讨不同临床分级慢性阻塞性肺疾病（COPD）患者经过长期家庭氧疗（LTOT）后肺功能变化情况.方法 选取220例COPD患者按照肺功能分级不同分为四组,所有患者均进行长期家庭氧疗,四年后复测所有患者的肺功能及相关生化、动脉血气指标.结果 四年后肺功能I、Ⅱ级患者的FEV1、FEV1/FVC%、FEV1%预计值及日间SaO2有下降趋势,且有统计学意义（P＜0.05）.而在肺功能Ⅲ、Ⅳ级患者中上述指标然也有下降趋势,但这种趋势无统计学差异.结论长期家庭氧疗对于所有COPD患者均有益处,尤其对于肺功能Ⅲ、Ⅳ级患者其延缓肺功能恶化的作用更为显著.     

Lung function and exhaled nitric oxide levels in infants developing chronic lung disease

Chronic lung disease (CLD) is a common outcome of neonatal intensive care. To determine whether the results of serial exhaled nitric oxide (eNO) measurements during the perinatal period differed between infants who did and did not develop CLD. In addition, we wished to assess whether eNO results were more predictive of CLD development than lung function test results or readily available clinical data (gestational age and birthweight). The patients were 24 infants with a median gestational age of 27 (range 25-31) weeks. Measurements of eNO levels, functional residual capacity (FRC), and compliance of the respiratory system (CRS) were attempted on postnatal days 1, 3, 5, 7, 14, and 28 days. The 12 infants who developed CLD were of significantly lower birthweight and gestational age than the rest of the cohort; in addition, they had lower median FRC (P < 0.02) and CRS (P < 0.02) results, but not higher eNO levels, in the first week after birth. Construction of receiver operator characteristic (ROC) curves demonstrated that the CRS and FRC results on Day 3 were the best predictors of CLD development; the areas under the ROC curves were 0.94 and 0.91, respectively. Early lung function test results, but not eNO levels, are useful in predicting CLD development, but are not significantly better than birthweight.     

Neonatal chronic lung disease,oxygen dependency,and a family history of asthma

We examined the relationship between a family history of asthma (FHA), neonatal chronic lung disease (CLD), and oxygen dependency in an inception cohort study of all 24-to 30-week gestation infants admitted to the sole tertiary perinatal center in Western Australia. One hundred and forty-four infants were admitted during the study period; 116 had data analyzed, I12 of whom survived to discharge. Respiratory morbidity was common and the prevalence increased with decreasing gestation. Hyaline membrane disease (HMD) occurred in 92 (79%) and CLD (oxygen dependency at 28 days) in 62 (53%); 35 (30%) were oxygen dependent at 36 weeks corrected age, and 16(14%) were oxygen dependent at term. Thirty-two infants had an FHA which was equally distributed between those infants with and without CLD. Infants with an FHA were more likely to be oxygen dependent at term (relative risk 4.4; 95% Cl 1.7,11.1). Thirty-eight percent of mothers smoked; 68% of their infants developed HMD compared to 89% of those whose mothers did not smoke. Logistic regression identified GA < 28 weeks (OR 7.3; 95% Cl 1.4,39), severe HMD (OR 4.8; 95% Cl 1.1,22), and FHA (OR 11.O; 95% Cl 2.3,53) as the only factors associated with an increased risk of being oxygen dependent at term. The duration of supplemental oxygen in infants with CLD was significantly related to decreasing gestation, greater degree of barotrauma, presence of HMD, pregnancy-induced hypertension in the mother, duration of patent ductus arteriosus, and an FHA. An FHA may worsen chronic lung disease in the neonate, but is not involved as a causal factor. Clinicians should be aware of its influence on duration of oxygen supplementation when counselling parents of very preterm infants. Pediatr Pulmonol. 1995; 20:277–283 . © 1995 Wiley-Liss, Inc.     

Effects of salbutamol delivery from a metered dose inhaler versus jet nebulizer on dynamic lung mechanics in very preterm infants with chronic lung disease

Treatment of chronic lung disease of prematurity requires effective aerosol delivery of different therapeutic agents. Aerosols can be generated by a metered dose inhaler (MDI) or a jet nebulizer. An MDI combined with a spacer device is easier to use and avoids undesirable effects noted in conjunction with jet nebulization. We compared the clinical effectiveness of 200 μg (2 puffs) salbutamol delivered from an MDI in conjunction with a valved spacer device (Aerochamber®), and 600 μg given via jet nebulizer (PariBaby®) on 2 consecutive days, the order being randomized. Thirteen spontaneously breathing very preterm infants [mean (SD) gestational age 27.2 (1.8) weeks; birth weight 0.90 (0.34) kg] were studied at a corrected age of 37 (2.3) weeks. Mean (SD) study weight was 1.83 (0.38) kg. Dynamic lung compliance and resistance were determined from measurements of flows, volumes, and transpulmonary pressures, using a pneumotachometer and a small esophageal microtransducer catheter before and 20 min after salbutamol application. Baseline values before salbutamol administration were similar on both occasions: the mean (SD) compliance was 7.7 (3.0) mL · kPa⁻¹ · kg⁻¹ pre-MDI plus-spacer and 8.4 (3.1) pre-jet nebulizer; the resistance was 10.4 (4.0) kPa · L⁻¹ · s pre-MDI plus-spacer and 9.7 (3.4) pre-jet nebulizer. Following salbutamol, compliance did not change significantly with either MDI plus spacer or jet nebulizer. Resistance fell significantly with MDI plus spacer (mean −2.2; 99.9% CI −0.35, −4.35) and jet nebulizer (−2.4; 99% CI −0.39, −4.42). We conclude that even in small preterm infants 200 μg salbutamol via MDI plus spacer improves dynamic resistance as effectively as 600 μg via jet nebulizer and may therefore be a preferable mode of aerosol administration. Pediatr. Pulmonol. 1997; 23:442–448. © 1997 Wiley-Liss, Inc.