PubMed Health⌕ Search

Biomedical subjects

M E Fletcher

Publications and source records attributed to M E Fletcher.

At least 19 recordsLinked to original sources
PubMed2001

Airway function at one year: association with premorbid airway function, wheezing, and maternal smoking.

BACKGROUND: Impaired growth and development of the respiratory system during fetal and early postnatal life may have important implications for lung development and later lung health. The aim of this study was to examine the association of diminished premorbid airway function, prior wheezing, and maternal smoking with airway function at 1 year of age. METHODS: Respiratory function was measured at the end of the first year in 100 of 108 healthy term infants (93%) in whom similar measurements had been undertaken prior to any respiratory illness at 8 weeks. Physician diagnosed wheezing episodes were identified retrospectively from medical records. RESULTS: At 1 year specific airway conductance during end expiration (sGawEE; /s/kPa) was significantly diminished in those infants with prior wheezing (95% CI wheeze/no wheeze -0.76 to -0.14), mothers who smoked (95% CI smoke/no smoke -0.81 to -0.27), a family history of asthma (95% CI family history/no family history -0.62 to 0.00), or diminished premorbid sGawEE (95% CI -0.13 to -0.43/s/kPa per unit reduction sGawEE at 8 weeks). In a multivariate model only maternal smoking and diminished premorbid sGawEE were independently associated with diminished sGawEE at 1 year. CONCLUSIONS: Diminished airway function at the end of the first year appears to be mediated by impaired airway development during early life as well as by exposure to maternal smoking. These findings are consistent with the hypothesis that, at a population level, diminished premorbid airway function provides the link between wheezing lower respiratory illness and diminished airway function at 1 year. Maternal smoking remains an important and avoidable cause of impaired airway development and function in infancy.

Airway Resistance↗
PubMed2000

Early asthma prophylaxis, natural history, skeletal development and economy (EASE): a pilot randomised controlled trial.

OBJECTIVES: (1) To establish recruitment rates of newly presenting asthmatic children. (2) To establish acceptability of study protocols. (3) To pilot age-specific quality of life (QoL) assessment. (4) To assess short-term (6 months) outcomes of inhaled corticosteroids (ICS) treatment. (5) To refine sample size calculations for a definitive study. DESIGN: A randomised pragmatic longitudinal trial design was used, with no blinding or placebo, to examine early ICS introduction similar to its use in practice. Subjects were assessed at entry, 3 and 6 months. SETTING: Subjects were recruited from six general practices. Children under 6 years were assessed at the Craig Research and Investigation Unit, Royal Aberdeen Children's Hospital, or their family home, and subjects 6 years and over were assessed at their general practice. SUBJECTS: Children (aged 6 months-16 years) with symptoms suggestive of asthma/wheeze that had commenced no longer than 12 months before were identified retrospectively and prospectively from general practices. Subjects were also required to be naïve to prophylactic therapy with no other lung disease/concomitant illness. INTERVENTIONS: Subjects were randomised to ss2-agonist (ss2-only group) or ss2-agonist and ICS (ICS group) for 6 months. Physicians could later prescribe ICS in controls if needed. MAIN OUTCOME MEASURES: (1) Pulmonary function. (2) Asthma symptom diary. (3) Symptomatic health status questionnaire. (4) Caregiver's and child's QoL. (5) Growth. (6) Bone mass. (7) Bone turnover. (8) Economic issues. RESULTS: Of over 15,000 children yielded from general practice records, 11% had symptoms suggestive of asthma/wheeze, and two-thirds of these already used ICS. Of the remaining, 141 subjects met the criterion of early asthma, and 86 were randomised. Two-thirds of those randomised were < 6 years old, the males:females ratio was 2:1, and 67% had a family history of atopy. RESULTS - PHYSIOLOGICAL DEVELOPMENT: Pulmonary function did not significantly improve in the older children. Although tidal breathing measures in the pre-school children were significantly higher at 6 months in the ss2-only group, there was great variability. Incidence of wheeze and night-time cough reduced equally in both groups. Reduction of night-time symptom score and reliever use, and increase in symptom-free days were only significant in the ss2-only group. No significant differences were found in growth and bone mass between the two groups, but bone metabolism was significantly reduced at 6 months in the ICS group. RESULTS - PSYCHOLOGICAL DEVELOPMENT: The caregiver's QoL questionnaire was sensitive to child symptom changes over 3 months, but absolute impact of child symptoms on their QoL varied, whereas the child-centred questionnaire was not sensitive to change. RESULTS - ECONOMICS: There were no significant differences in medical consultation costs between the groups, but, as expected, prescription costs in the ICS group were higher over 6 months. Combined healthcare costs were significantly higher for patients assigned to ICS, but there were no significant differences in any effectiveness measures between the groups. CONCLUSIONS: Most (96%) of the proposed sample was recruited, and the low drop-out rate (8%) demonstrated acceptability of the study protocol. Most children first presenting with symptoms suggestive of asthma were < 6 years old and represented a group biased towards mild to moderate asthma, or virally induced wheeze. The caregiver's QoL questionnaire was found to better reflect a child's symptom changes than a child-centred instrument. In the short term, no adverse effects were seen on growth, but ICS treatment significantly reduced bone metabolism. Most of the young children with asthma/wheeze improved over time with ss2-agonist treatment alone, and clinical benefits of early ICS intervention amongst these children were not detected; however, there was inadequate power in this pilot study to establish this. (AB

Adolescent↗
PubMed1999

Impaired airway function and wheezing in infancy: the influence of maternal smoking and a genetic predisposition to asthma.

This prospective community-based study of infants born in inner London was undertaken to examine the association between premorbid airway function and subsequent wheezing in the first year of life and to explore the influence on this association of a family history of asthma and maternal smoking during pregnancy. Healthy Caucasian term infants were recruited shortly after birth, and physician-diagnosed wheezing episodes were identified retrospectively from medical records. Specific airway conductance was determined from plethysmographic measurements of lung volume and airway resistance, before 13 wk and prior to any respiratory illness, in 101 infants, 28 of whom experienced at least one episode of wheezing during the first year. Mean (SD) specific airway conductance was significantly diminished in infants who subsequently wheezed: 2.02 (1.07) s-1. kPa-1 and 2.60 (0.93) s-1. kPa-1, respectively (p < 0.05), and in those with a first-degree relative with asthma: 1.98 (0.83) s-1. kPa-1 and 2.60 (1.0) s-1. kPa-1, respectively (p < 0.05), but not in those whose mothers smoked during pregnancy, in whom airway resistance was, however, significantly elevated (p < 0.05). The odds ratio (95% confidence interval [CI]) for wheezing was 2.1 (1.1 to 3.8) for every unit (s-1. kPa-1) decline in specific airway conductance (p = 0.02). After adjustment for premorbid airway function, the odds of wheezing were significantly increased in those with a family history of asthma (4. 3; 95% CI, 1.3 to 13.8; p = 0.016) and those exposed to maternal smoking during pregnancy (4.9; 95% CI, 1.6 to 15.0; p = 0.005). Our findings confirm previous reports that impaired premorbid airway function precedes and predicts wheezing in the first year. Among those with a genetic predisposition to asthma, alterations in airway geometry or tone may increase susceptibility to wheezing. Maternal smoking has important and potentially preventable adverse effects on somatic growth and respiratory morbidity in early life.

Airway Resistance↗
PubMed1997

Infant respiratory function after RSV-proven bronchiolitis.

The mechanisms underlying the increased risk of wheezing in early childhood following acute bronchiolitis in infancy remain unclear. Previous studies have reported significant abnormalities in infant respiratory function after clinical recovery from bronchiolitis, but are difficult to interpret because of the frequent omission of a concurrent comparison group. Respiratory function was compared within pairs of previously healthy full-term caucasian infants admitted with a first episode of acute bronchiolitis to an inner London hospital, and age- and sex-matched control infants without prior wheezing, asthma, or lower respiratory illness who were recruited from local general practices. Respiratory function was measured in 29 control and 29 asymptomatic index infants, with measurements in the latter done at a median interval of 36 wk (range: 16 to 49 wk) after admission, when 16 (55%) had experienced subsequent wheezing. Index infants tended to be autumn-born and of shorter gestation than control infants, to have younger mothers, and to have been exposed to tobacco smoke. There were no statistically significant differences in plethysmographic FRC, initial inspiratory airway resistance (Raw), or respiratory system compliance (mean [index minus control] within-pair difference [95% confidence interval]: -11 ml [-29, 7 ml]; -0.2 kPa/L/s [-0.7, 0.4 kPa/L/s]; -8 ml/kPa [-21, 4 ml/kPa], respectively), but respiratory rate and time to peak tidal flow as a proportion of total expiratory time (tPTEF:tE) were significantly diminished in index as compared with control infants (-4.0 breaths/min [-7.6, -0.4 breaths/min], versus -0.035 [-0.066, -0.005], respectively). These findings suggest a better prognosis for infant lung function after acute bronchiolitis than reported previously. Longitudinal studies are needed to clarify whether subclinical alterations in airway function precede acute bronchiolitis.

Acute Disease↗
PubMed1995

The single breath test in neonates: does pressurization of the pneumotachograph make a difference?

The single breath test for the measurement of respiratory system resistance and compliance in newborns consists of an end inspiratory occlusion which is subsequently released, allowing expiration to proceed through a pneumotachograph (PNT). The measured flow is then integrated to give volume. The simplicity of the test is one of the major reasons for its popularity. However, some investigators have cautioned against the use of an occlusion distal to the PNT because pressurization of the PNT may introduce artifacts in the flow measurement. Despite this caution, many commercial systems use a pressurized PNT. This study investigated the errors that would result from pressurization of the PNT by providing a step function of flow to two infant PNTs, a Fleisch #0 and a Hans Rudolph 4500, in the unpressurized and pressurized state. In each case there was an initial rapid rise of the flow signal, followed by some overshoot and oscillations that rapidly died out. The overshoot and oscillations for the Hans Rudolph PNT were greater when pressurized whereas pressurization had little effect on the Fleisch PNT. Unpressurized, the two were similar. In either case, the artifact introduced by pressurization of the PNT died out so quickly that it would have little effect on any measurement in an infant.

Airway Obstruction↗
PubMed1995

Comparison of single-breath and plethysmographic measurements of resistance in infancy.

Single-breath technique (SBT) measurements of total respiratory resistance (Rrs) were compared with plethysmographic measurements of airway resistance (Raw) in healthy infants < or = 13 wk of age (Group 1; n = 49) and > 13 wk of age (Group 2; n = 37) and in infants > 13 wk of age with prior wheeze (Group 3; n = 49). A significantly higher percentage of Rrs (19%) than of Raw (2%) measurements were technically unsatisfactory, alinearity of the flow-volume curve accounting for 54% of Rrs failures. Although both Rrs and Raw were significantly higher in Group 3 infants, between-subject variability was wide in all groups. Rrs was significantly higher than initial expiratory (IE) Raw in all groups. Mean difference Rrs-IE Raw (95% CI) values were 1.98 (1.51, 2.48), 1.29 (0.96, 1.62), and 1.97 (1.56, 2.38) kPa.L-1.s for Groups 1, 2, and 3, respectively. Significant but smaller differences were seen for end-expiratory (EE) Raw in Groups 1 and 2 but not in Group 3. Mean difference Rrs-EE Raw (95% CI) values were 0.68 (0.11, 1.26), 0.55 (0.19, 0.92), and 0.31 (-0.06, 0.69) kPa.L-1.s for Groups 1, 2, and 3, respectively. Despite wide between-subject variability in Rrs and a relatively high failure rate, the SBT is simple to use, and it may be applicable to epidemiologic studies. However, clinical applications in individual infants may be limited by failure to detect the dynamic changes in resistance throughout the breath evident from plethysmographic studies.

Airway Resistance↗
PubMed1994

The relationship between tPTEF:tE and specific airway conductance in infancy.

This study examines the association between the time taken to achieve peak tidal expiratory flow as a proportion of total expiratory time (tPTEF:tE) and specific airways conductance (SGaw) in healthy infants and those with prior physician diagnosed, associated, lower respiratory illness with wheezing (prior LRI) during the first year of life. We compared tPTEF:tE and SGaw, the latter estimated during both initial inspiration (ll) and end-expiration (EE), in 168 infants (94 males), measured on 220 occasions. Mean (range) tPTEF:tE was 0.321 (0.150-0.522) in 73 healthy infants aged less than 3 months (mean, 7.8 weeks), in whom mean (range) EE SGaw and plethysmographic thoracic gas volume at functional residual capacity (FRCpleth) were 2.47 s-1 kPa-1 (0.6-5.8) and 141 mL (87-204), respectively. Both tPTEF:tE and EE SGaw were significantly lower in older infants with prior LRI (n = 79; mean age, 50.0 weeks) compared to a similarly aged group of healthy infants (n = 68; mean age, 48.5 weeks), the mean difference [95% confidence intervals (CI)] being -0.039 (-0.013, -0.064) and -0.48 s-1 kPa-1 (-0.24, -0.72), respectively. A significant but weak association between tPTEF:tE and EE SGaw was found among infants above 3 months of age, irrespective of prior wheezing status. However, this relationship was not significant in healthy younger infants, in whom a significant but weak association with FRCpleth was found. Further work is needed to elucidate the factors influencing tidal expiratory flow patterns in infancy.

Age Factors↗
PubMed1994

Hering-Breuer reflex and respiratory system compliance in the first year of life: a longitudinal study.

The airway occlusion technique for measuring passive respiratory mechanics in infants relies on an ability to evoke the Hering-Breuer lung inflation reflex (HBR). However, there is conflicting evidence regarding the persistence of the HBR beyond the early newborn period. This study was designed to assess maturational changes in HBR activity and passive total respiratory system compliance (Crs) in healthy infants during the 1st yr of life. The strength of the HBR was assessed from the relative change in expiratory time (TE) after brief end-inspiratory airway occlusions compared with resting TE during spontaneous breathing. Crs was measured using the multiple-occlusion technique. Paired measurements of HBR activity and Crs were obtained during sedated sleep in 30 infants at 4-8 wk and at 1 yr of age. Significant HBR activity during tidal breathing persisted throughout the 1st yr of life, with TE increasing during occlusion by at least 26% in every infant. However, the relative strength of the reflex response decreased from a mean of 88.3% (range, 34-160%) at approximately 6 wk to 50.3% (range, 26-125%) by 1 yr of age (P < 0.001). All infants showed an increase in Crs with age, with mean Crs increasing from 60.1 +/- 8.9 (SD) to 149.0 +/- 20.6 ml/kPa between 6 wk and 1 yr. However, there was no apparent relationship between the magnitude of decline in HBR response and the age-related changes in Crs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Comparison of nitrogen washout and plethysmographic measurements of lung volume in healthy infants.

Functional residual capacity (FRC), the only lung volume to be assessed routinely in infants, can be measured using plethysmography or gas dilution. Although it is well recognized that both methods yield similar FRC values in healthy adults, gas dilution techniques have consistently produced lower values in healthy infants when compared with plethysmography. However, interpretation of this difference is difficult since data comparing the different techniques within the same infants have rarely been reported. We performed paired measurements of FRC using an automated open-circuit nitrogen washout technique (FRCN2) and whole-body plethysmography (FRCpleth) in 11 healthy infants with a median age of 12 months (range, 2 to 18 months). The mean (SD) FRC was 21.7 (4.0) ml/kg for the N2 washout and 25.6 (4.9) ml/kg for plethysmography. The mean within-subject difference between FRCN2 and FRCpleth was 3.9 (range, -0.3 to 7.2) ml/kg (p = 0.001). Both N2 washout and plethysmography yielded reproducible results, with the mean of the coefficients of variation (CV) being 3.6 and 3.9%, respectively. The results from these paired measurements support previously reported data from separate populations of infants which suggest that gas dilution techniques consistently yield smaller values for FRC than do those measured by plethysmography.

Female↗
PubMed1992

Respiratory compliance in infants--a preliminary evaluation of the multiple interrupter technique.

Measurements of total respiratory system compliance (Crs) using the multiple occlusion technique (MOT) in spontaneously breathing infants can be difficult to interpret in the presence of an unstable end-expiratory level. Similarly, measurements using the passive flow volume technique (PFV) are invalidated if there is alinearity of the expiratory time constant (Trs), irrespective of respiratory effort. For possibly overcoming these problems, we assessed the feasibility of a technique using multiple interruptions of of a single expiration (MIT), obtaining several pairs of volume-pressure data, from one expiration, which relate to a single end-expiratory level. Crs was measured in 16 infants aged 0.5 to 20 months using the MOT, MIT, and PFV technique. The MOT and the MIT each failed in one (different) infant, both succeeding where the other failed. The PFV technique failed in five infants in whom no acceptable plateau of airway pressure during occlusion and no Trs could be obtained from a single breath. Failure to obtain a linear Trs was accompanied by failure of the MIT in only one infant. Individual differences between the MIT and the MOT were less than 9%. However, the PFV measurements varied from -16.3% and +25.7% of the values from MIT or MOT. The greatest differences between Crs values coincided with the greatest differences between volume intercepts of the extrapolated volume-pressure (MOT, MIT) and flow-volume (PFV) data. From this preliminary study, the MIT proved as successful as the MOT, requiring fewer occluded breaths to measure Crs. In infants with a rapid respiratory rate, the data from several expirations can be merged and analyzed as for the MOT.

Humans↗
PubMed1991

Influence of sedation on the Hering-Breuer inflation reflex in healthy infants.

The airway occlusion technique for measuring passive respiratory mechanics in infants relies on an ability to evoke the Hering-Breuer inflation reflex (HBR). However, the persistence of this reflex beyond the early newborn period remains controversial. We have recently demonstrated that there is no change in the strength of this reflex during the first two months of life in healthy infants during natural sleep. Measurements beyond this immediate newborn period are difficult without sedation, but it is unclear whether sedation itself may influence this reflex. To investigate the influence of sedation, the HBR was measured in 66 healthy, full-term infants aged 4-8 weeks. Thirty-three infants were measured during natural sleep, and 33 after triclofos sodium sedation (75 mg.kg-1). The strength of the HBR was assessed from the change in expiratory time (TE) following brief end-inspiratory airway occlusion, as compared to TE during spontaneous breathing. The mean increase in TE following occlusion was 89.45% (SD, 29.8; range, 44-175) in infants sleeping naturally, and 92.42% (SD, 31.2; range, 34-179) in sedated infants. Using unpaired t tests, no statistically significant difference was found between groups (P = 0.7516). We conclude that the strength of the HBR in healthy infants is not influenced by sedation with triclofos sodium, in doses normally used for lung function testing.

Female↗
PubMed1991

Assessment of a hygroscopic heat and moisture exchanger for paediatric use.

A laboratory study of a widely available heat and moisture exchanger marketed for paediatric use was undertaken. The deadspace, measured by volume displacement, was 12 ml, similar to that of a standard catheter mount for paediatric use. Pressure drop across the device was measured at several different flows in five samples of the device in both the dry and wet state. Calculated resistance proved to be markedly lower when compared with that of other anaesthetic equipment such as tracheal tubes, and with similar humidification devices for paediatric use.

Anesthesiology↗
PubMed1991

Respiratory compliance during sedation, anesthesia, and paralysis in infants and young children.

Although total respiratory compliance (Crs) has been shown to fall in adults on induction of halothane anesthesia, no successful paired studies have been reported in children. The multiple occlusion technique was used to measure Crs in 17 infants and young children during sedated sleep (CrsS) and shortly after, following induction of halothane anesthesia (CrsA). Crs fell in all but one infant after induction of anesthesia, with a mean fall of 34.7% (range 0-58%). This was accompanied by a reduction in tidal volume and increase in frequency in every case. In 7 of the 17 children, who were to be paralyzed for surgical purposes, Crs was also measured in this anesthetized-paralyzed state. When tidal volume administered during manual ventilation was similar to that observed during measurement of CrsA, Crs during this low-volume ventilation was similar to CrsA. When tidal volume was increased and Crs remeasured, there was a significant increase in every case, with the high-volume Crs within 10% of CrsS in all but one child, in whom there was a 31.4% increase with respect to CrsS. Changes in tidal volume accounted for approximately 50% of the variability in each state. These results demonstrate a highly significant fall in Crs in infants and young children after induction of halothane anesthesia. In addition it appears that this reduction in Crs can be reversed by paralyzing the child and manually ventilating with tidal volumes approximating those seen during sedation.

Anesthesia↗
PubMed1990

Total respiratory compliance in infants and young children with congenital heart disease.

The multiple occlusion technique was used to measure total respiratory system compliance (Crs) in 62 infants and young children with congenital heart disease (age range, 2 days to 2 years). Measurements were found to be reproducible in nine infants in whom repeat measurements were possible (maximum deviation between measurements less than 10%). The incidence of failure to obtain accurate results was no greater than when studying infants without cardiopulmonary disease. However, in the presence of severe growth retardation or alinearity of volume-pressure data, results may be difficult to interpret in individuals. Results of Crs were related to non-invasive assessments of cardiac disease severity using chest radiography and echocardiography. After the effects of growth had been taken into account, a significant negative relationship was found between Crs and the right pulmonary artery to aortic ratio, which reflects pulmonary vascular engorgement (P = 0.003, R2 = -0.40). However, no significant relationship was found between Crs and chest X-ray score (P = 0.27).

Aorta↗
PubMed1990

Influence of tidal volume on respiratory compliance in anesthetized infants and young children.

Recent studies have suggested a close association between total respiratory compliance (Crs) and tidal volume in anesthetized paralyzed infants who are being artificially ventilated. To investigate this further, the multiple occlusion technique was used to measure Crs in 20 anesthetized infants and young children (aged 1-25 mo) before elective surgery. Measurements were made after intubation 1) during spontaneous breathing (SB), 2) after administration of a non-depolarizing muscle relaxant with tidal volume and frequency mimicking that during SB, and 3) with the child still paralyzed but tidal volume approximately double that during SB. Compared with values obtained during SB, there was no significant change in Crs after paralysis when ventilation matched the child's own pattern (P greater than 0.2). When ventilated with the larger tidal volumes, the infants showed a highly significant increase in Crs (mean 62%, range 14-158%, P less than 0.0001). These results may have implications not only for studies performed during anesthesia but also when infants were monitored in the intensive care setting. Values of Crs obtained in ventilated infants may reflect both the mechanical behavior of the respiratory system and the pattern of ventilation at the time of measurement.

Anesthesia↗
PubMed1989

Total respiratory compliance during anaesthesia in infants and young children.

The multiple occlusion technique was used to study the effects of paralysis on ventilatory mechanics during anaesthesia. Total respiratory compliance (Crs) was measured during spontaneous breathing and following neuromuscular block with controlled ventilation in 23 infants. There was marked variation in response to paralysis: some infants demonstrated no change in Crs between the two states; others had values of Crs which were significantly higher during paralysis with controlled ventilation than during spontaneous breathing. A possible cause of these differences may be the type of controlled ventilation given during paralysis, with tidal volume directly influencing values of Crs obtained. The results of this study suggest that values of Crs obtained during spontaneous breathing and paralysis should not be used interchangeably until further studies have been performed to assess factors influencing Crs during controlled ventilation.

Anesthesia, General↗