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Biomedical subjects

P M Gustafsson

Publications and source records attributed to P M Gustafsson.

At least 19 recordsLinked to original sources

Poor asthma control in children: evidence from epidemiological surveys and implications for clinical practice.

The objectives of this study is to compile current knowledge about asthma control in children in relation to goals proposed in international guidelines, to elucidate the factors associated with insufficient asthma control and to address the implications for clinical practice. Review of recent worldwide large population epidemiological surveys and clinical asthma studies of more than 20,000 children are the methods used in this study. The studies report high frequencies of sleep disturbances, emergency visits, school absence and limitations of physical activity due to asthma. Only a small percentage of children with asthma reach the goals of good asthma control set out by Global Initiative for Asthma (GINA). There is evidence of underuse of inhaled corticosteroids even in children with moderate or severe persistent asthma and over-reliance on short-acting beta(2)-agonist rescue medication. Both parents and physicians generally overestimate asthma control and have low expectations about the level of achievable control. Many children with asthma are not being managed in accordance with guideline recommendations, and asthma management practices vary widely between countries. Asthma control falls short of guideline recommendations in large proportions of children with asthma worldwide. Simple methods for assessing asthma control in clinical practice are needed. Treatment goals based on raised expectations should be established in partnership with the asthmatic child and the parents. Effective anti-inflammatory treatment should be used more frequently, and patients should be reviewed regularly.

Adolescent↗

Peripheral airway involvement in asthma assessed by single-breath SF6 and He washout.

The aim of the study was to assess how deep into the acinar region the airway response to cold dry-air hyperventilation challenge (CACh) reaches in subjects with asthma of different severity. Peripheral airway function was measured using a single-breath sulphur hexafluoride (SF6) and helium (He) washout test and overall airway function by forced expiratory volume in one second (FEV1) at rest, after CACh and beta2-therapy in 55 adults with a history of asthma. The normalised phase-III slopes (SnIII) for SF6 and He were used to assess peripheral airway obstruction and the (SF6-He) SnIII difference to indicate where obstruction occurred. While a greater He versus SF6 slope increase indicates a response close to the acinar entrance, the reverse indicates a response deeper into the acinar airspaces. Twelve subjects had a major fall in FEV1 (> or = 20%) after CACh, 16 a minor fall (10-19%), and 27 did not react. Resting He and SF6 SnIII were significantly greater in major responders with respect to minor and nonresponders, while resting FEV1 did not differ between the three groups. The major responders showed marked increases of He and SF6 SnIII after CACh, with greater increase for He resulting in a negative (SF6-He) SnIII difference. To conclude, airways close to the acinar entrance participate in the overall airway response to cold-air challenge in asthmatic adults with marked airway hyperresponsiveness to cold, dry air.

Adrenergic beta-Agonists↗

Evaluation of ventilation maldistribution as an early indicator of lung disease in children with cystic fibrosis.

Many children with cystic fibrosis (CF), receiving modern, aggressive CF care, have normal spirometry results. This study aimed to see if homogeneity of ventilation distribution is impaired early in the course of CF lung disease, and if ventilation inhomogeneity is a more frequent finding than abnormal spirometry in children benefiting from modern CF care. The study compared spirometry findings to two indices of ventilation inhomogeneity (mixing ratio (MR) and lung clearance index (LCI)) from multiple-breath inert gas washout in 43 children with CF, aged 3-18 yrs, and 28 healthy children. In total, 10/43 CF subjects (23%) had reduced forced expiratory volume in one second (FEV1) and 14/34 (41%) showed abnormal maximum expiratory flow at 25% of forced vital capacity (MEF25). In contrast, MR was abnormal in 31/43 (72%) and LCI in 27/43 (63%). MR was abnormal in 22/33 CF subjects with normal FEV1, versus 0/28 controls (p<0.001), and abnormal MR was found in 10/20 CF subjects with normal MEF25, versus 0/22 controls (p<0.001). Nine of the 10 CF subjects with reduced FEV1 and 12/14 with abnormal MEF25 showed abnormal MR. Inert gas washout discloses airway dysfunction in the majority of children with cystic fibrosis with normal lung function judged by spirometry. These findings suggest that multiple-breath inert gas washout is of greater value than spirometry in detecting early cystic fibrosis lung disease.

Adolescent↗

Asthma severity, allergy and lung function during young middle life in subjects with asthma in childhood.

The further course of asthma severity lung function, bronchial hyperresponsiveness (BHR) to cold air challenge (CACh), clinical allergies and allergic sensitization in young middle adulthood was studied in a cohort of 55 subjects with childhood asthma. All subjects (27 females) have attended all five previous and the current follow-up visit, undertaken at a mean age of 35 years. Twelve subjects (22%) reported no current asthma, 28 (51%) mild/intermittent, and 15 (27%) moderate/severe asthma. Asthma severity changed little in the individual subjects over the last 5-year period. Females continued to have higher asthma severity scores than the males, but the previously noted lower resting and post-bronchodilator % predicted FEV1 in females was not confirmed now. Pathological BHR to CACh tended to be more common among the males. Forty-four subjects were still allergic to animal danders and 35 to pollens. Sensitization rates (skin prick test or RAST) were similar to those recorded 5 years earlier and there was no clear evidence of tolerance developing. Five subjects have never shown evidence of allergy or sensitization. The extent of sensitization to animal danders showed statistically significant relationships to asthma severity and BHR to CACh. Social development and professional careers continued to be good.

Adult↗

Effects of hypergravity and anti-G suit pressure on intraregional ventilation distribution during VC breaths.

The effects of increased gravity in the head-to-foot direction (+G(z)) and pressurization of an anti-G suit (AGS) on total and intraregional intra-acinar ventilation inhomogeneity were explored in 10 healthy male subjects. They performed vital capacity (VC) single-breath washin/washouts of SF(6) and He in +1, +2, or +3 G(z) in a human centrifuge, with an AGS pressurized to 0, 6, or 12 kPa. The phase III slopes for SF(6) and He over 25-75% of the expired VC were used as markers of total ventilation inhomogeneity, and the (SF(6) -- He) slopes were used as indicators of intraregional intra-acinar inhomogeneity. SF(6) and He phase III slopes increased proportionally with increasing gravity, but the (SF(6) -- He) slopes remained unchanged. AGS pressurization did not change SF(6) or He slopes significantly but resulted in increased (SF(6) -- He) slope differences at 12 kPa. In conclusion, hypergravity increases overall but not intraregional intra-acinar inhomogeneity during VC breaths. AGS pressurization provokes increased intraregional intra-acinar ventilation inhomogeneity, presumably reflecting the consequences of basilar pulmonary vessel engorgement in combination with compression of the basilar lung regions.

Adult↗

[Children with asthma followed up for 21 years. Reduced severity, but patients seldom grow out of asthma by adulthood].

The course of asthma severity, clinical allergies, allergic sensitization, lung function, changes in living conditions and social outcome were studied prospectively in 55 asthmatic children for 21 years, from a mean age of 9 to 30 years. Asthma severity improved, but only 16 percent were in remission at the final follow-up. After adolescence, clinical improvement continued among males but not among females. Lung function showed a similar gender difference with respect to clinical course. Generally, clinical allergies and sensitization to pollens and animal danders persisted in adulthood. In adulthood, asthma severity and degree of bronchial hyperresponsiveness correlated with the extent of sensitization to furred animals.

Adolescent↗

Ventilation inhomogeneity assessed by nitrogen washout and ventilation-perfusion mismatch by capnography in stable and induced airway obstruction.

Few studies have been published on gas distribution in the lung during acute and stable airway obstruction in children. Multiple breath nitrogen (N(2)) washout is an established method for assessing ventilation inhomogeneity, while the tidal breathing capnogram may be used as an indicator of ventilation-perfusion (V(')(A)/Q) mismatch. We hypothesized that significant V(')(A)/Q mismatch is not seen in stable airway obstruction unless obstruction is severe, and that stable and induced airway obstruction of similar severity would result in different degrees of V(')(A)/Q mismatch. To test this hypothesis, we performed spirometry measurements of forced expiratory volume in 1 sec (FEV(1)), multiple breath N(2) washout, and tidal breathing capnography in 11 young patients (9-30 years) with cystic fibrosis, 37 asthmatic patients (8-18 years), and 34 healthy subjects (7-20 years). Lung function was measured at rest, after airway obstruction induced by cold dry air hyperventilation or methacholine challenge, and after beta(2)-agonist treatment. V(')(A)/Q mismatch was assessed from the slopes of the phases II and III of the capnogram. We observed a normal capnogram during stable obstruction of moderate severity despite significant ventilation inhomogeneity. In patients with severe stable obstruction and in those with induced airway obstruction significant ventilation inhomogeneity and pathological capnograms were seen. Induced airway obstruction, resulted in a more pathological capnogram than stable obstruction of similar severity. beta(2)-agonist treatment reduced ventilation inhomogeneity, but did not improve the capnogram. Our findings are compatible with the presence of an efficient pulmonary blood flow regulatory mechanism that adequately compensates for chronic ventilation inhomogeneity of moderate severity, but not for severe or sudden airway obstruction.

Adolescent↗

Asthma from childhood to adulthood: course and outcome of lung function.

Lung function (FEV1 before and after bronchodilatation) was studied prospectively over five visits in 55 asthmatic children (28 boys) from childhood to adulthood (age 30). At the last follow-up recordings were made at rest, after cold air challenge (CACh), and after bronchodilatation. Results were related to clinical asthma scoring and to sensitization to furred animals, as described in a companion paper. Lung function outcome was shown to be influenced by initial FEV1 (% predicted) and gender, but not by initial asthma severity or sensitization. FEV1 (% predicted) was higher in females than in males over the first two follow-ups, but the reverse was found over the subsequent visits. It deteriorated from childhood to adulthood in the females but improved in the males. In adulthood the females (for height 170 cm) had a steeper normalized annual fall in post-bronchodilator FEV1 than the males (55 +/- 38 vs. 25 +/- 36 ml; P = 0.006). The degree of bronchial hyperresponsiveness was associated significantly with asthma severity and the extent of sensitization to furred animals, but not with gender. The results indicate a better lung function outcome for asthmatic boys than for girls, confirming trends seen in clinical asthma severity. In adulthood the extent of sensitization to relevant perennial inhaled allergens significantly influences airway responsiveness and asthma severity, but not lung function.

Adolescent↗

Asthma from childhood to adulthood: asthma severity, allergies, sensitization, living conditions, gender influence and social consequences.

The course of asthma severity, clinical allergies, allergic sensitization, changes in living conditions and social outcome were studied prospectively over five follow-up visits from the mean age of 9 to 30 years in a cohort of 28 boys and 27 girls, selected randomly among asthmatic children attending a paediatric outpatient unit. Asthma severity improved from childhood to adulthood, judged by symptom and medication scores and by the number of hospital admissions, but only nine subjects (16%) had been free from symptoms and medication over the last year of follow-up. After adolescence, asthma continued to improve among the males but not among the females. This difference could not be explained by gender differences in the course of clinical allergies or sensitization (skin-prick-tests and RAST) to common inhaled allergens, or by differences in environmental or social conditions. Sensitization to relevant perennial inhaled allergens correlated with asthma severity during adulthood. In general, clinical allergies and sensitization to inhaled allergens adopted during childhood persisted into adulthood. Approximately 10% of the subjects never adopted a clinical allergy or a positive allergy test. The social outcome was good.

Adolescent↗

Breathing pattern variability during bronchial histamine and methacholine challenges in asthmatics.

Breathing pattern variability was determined in 10 asthmatic adolescents during repeated bronchial histamine and methacholine challenges (HiCh/MeCh). The purpose was to provide information on ventilatory control in asthmatics by comparing the variability of the various breathing pattern parameters at rest and during induced bronchial obstruction. Changes in variability during bronchial obstruction might be explained by either anxiety effects causing increased variability or by the minimization of the work of breathing causing decreased variability. Ventilation was monitored by respiratory inductive plethysmography in order to minimize the effects on the spontaneous pattern of breathing. Breath-to-breath and day-to-day variability were determined concerning respiratory frequency (fR), inspiratory tidal volume (VTI), inspiratory ventilation (V'I), inspiratory time to total cycle time ratio (TI/TTOT), mean inspiratory flow (VTI/TI, an index of ventilatory drive), rib cage fraction of VTI (VRC/VTI), and maximum compartmental amplitude to VTI ratio (MCA/VTI; an index of rib cage and abdominal phasing). No difference in any parameter was found regarding breath-to-breath coefficient of variation (CV = SD/mean) between recordings at baseline, after saline inhalation and after threshold dose of the provocative agents, i.e. > 20% fall in FEV1. Variability was less for MCA/VTI and VRC/VTI (mean CV 1.3 and 7.7%, respectively) than for TI/TTOT, fR, VTI/TI, VTI, and V'I (14.2, 15.8, 20.9, 22.2 and 21.1%, respectively) (P < 0.01). Likewise, the day-to-day variability did not differ in any parameter between recordings at baseline, after saline inhalation and after threshold dose. The variability was less for MCA/VTI (0.7%) than for TI/TTOT, VRC/VTI, V'I, VTI/TI, fR and VTI (7.1, 12.1, 12.8, 14.2, 13.0 and 15.4%) (P < 0.05). Furthermore, TI/TTOT was less variable than VTI (P < 0.05). Thus, the ventilatory pattern was quite reproducible on a day-to-day basis, despite considerable breath-to-breath variability. Ventilatory drive and tidal volumes were more variable than the rib cage and abdominal phasing, the respiratory timing and the rib cage fraction of tidal volume. The lack of difference in variability between rest and induced bronchial obstruction indicates that other factors than anxiety or minimization of the work of breathing are important for the control of respiration in asthmatics during bronchial challenge.

Administration, Inhalation↗

Hyperventilation during bronchial challenges in asthmatics: reproducibility and assessment of contributing factors.

Among asthmatics, the ventilatory response is heterogeneous during bronchial challenge. This study aimed to investigate the reproducibility of the response and to assess possible causes for hyperventilation. Repeated bronchial histamine and methacholine challenges (HiCh/MeCh) were performed in 10 asthmatic adolescents. Ventilation was monitored by respiratory inductive plethysmography (RIP), in order to minimally affect the spontaneous breathing pattern. FEV1 and the volume of trapped gas (measured as the volume of air mobilized by five maximal breaths after a multiple breath nitrogen washout to 2% N2), were used to assess mainly central and peripheral airways obstruction, respectively. When FEV1 had decreased by at least 20%, mean inspiratory flow (VTI/TI) increased by 21% and minute ventilation (V'I) by 21% and 23% during HiCh and MeCh, respectively (both P < 0.05). No correlation was found between the magnitude of the ventilatory response and either: the degree of FEV1 decline, the increase in gas trapping, SaO2 decline or the increase in dyspnoea score. Histamine challenge after beta 2-agonist pre-treatment was associated with increased ventilatory drive in one patient despite the absence of bronchial obstruction, indicating that histamine might directly stimulate afferent airway nerves which cause hyperventilation. The intra-individual variability of the ventilatory response (increase in V'I and VTI/TI) was more than 100% of the mean ventilatory response, while the variability of the bronchomotor response was about 25% of the mean bronchomotor response. Thus, during induced bronchial obstruction in asthmatics, the occurrence of hyperventilation and its intensity are not related to either the degree of central or peripheral airways obstruction, or to the degree of dyspnoea. The reproducibility of the ventilatory response is poor. The ventilatory response appears to be the result of a complex interaction between several afferent stimuli and central ventilatory control.

Administration, Inhalation↗

A method for measuring the CO2 dead space volume in facial visors and respiratory protective devices in human subjects.

The external CO2 dead space volume (Vd) in facial visors and respiratory protective devices is difficult, but important, to measure in human subjects. The lack of proper methods for its assessment has hampered the development of standards and the improvement of visor and device design. We have improved and evaluated a method for measuring Vd and the mean inspired fraction of CO2 (FI,CO2) in human subjects wearing facial visors or respiratory protective devices. The method is based on indirect measurements of inspiratory volumes using a calibrated respiratory inductive plethysmograph (RIP), and measurements of FCO2 with a mass spectrometer. The accuracy of the RIP method was assessed in eight subjects and its repeatability was studied during nasal and oral breathing, at rest and after bicycle ergometer work. We related the Vd,RIP results to two known external VdS (with the effective Vd equal to the geometric volume; 15 ml and 320 ml), through which the subjects breathed, using RIP and a pneumotachometer (PTM) simultaneously (Vd,RIP and Vd,PTM). The repeatability of Vd and mean FI,CO2 results was determined from duplicate recordings during the wearing of a welding visor. Initial RIP calibration was accepted if the inspiratory tidal volume error was < or = 10%. This resulted in an acceptable Vd,RIP error (< or = 20%; Vd = 320 ml) in six eight subjects. The validation technique allowed us to separate the Vd,RIP error into a volumetric error and an error related to CO2 measurement. Poor RIP volumetric accuracy over the initial portion of inspiration was detrimental to Vd accuracy. Using the welding visor, Vd and mean FI,CO2 were less at rest than after work and less during nasal breathing than during oral breathing. The intra-individual variability of Vd and mean FI,CO2 were lower during nasal breathing than during oral breathing. To summarize, the improved RIP based method can accurately (< or = 20% error) assess Vd and mean FI,CO2 in facial visors and respiratory protective devices in standardized work situations. A meticulous RIP calibration procedure and repeated validations of RIP volume and CO2 measurement accuracy must, however, be applied.

Adolescent↗

Pneumotachographic nitrogen washout method for measurement of the volume of trapped gas in the lungs.

A computerized pneumotachometric multiple breath N2-washout method for assessment of the volume of trapped gas in the lungs (VTGN2) is presented. The VTGN2 is measured as the volume of air mobilized from nonventilated lung spaces by five maximal breaths after a washout performed until the end-tidal nitrogen fraction is 0.02. The method demonstrated a good instrumental precision and the reproducibility of VTGN2 recordings in normal subjects was equal to that achieved with a previous VTGN2 method based on gas collection in bags. It was confirmed that gas trapping occurs in normal children during tidal breathing at functional residual capacity. In normal subjects VTGN2 was directly related to lung size. In 69 healthy children and adolescents VTGN2 showed a good correlation with vital capacity (r = 0.85; P < 0.001), of which it comprised 1.7 +/- 0.4% (mean +/- SD). Patients with bronchial asthma or cystic fibrosis investigated had pathological gas trapping with only a few exceptions; in several cases despite normal results at forced expiratory spirometry. The relative response of VTGN2 (reflecting peripheral airway obstruction) and forced expiratory volume in one second (FEV1) (reflecting conditions in central airways) to beta 2-agonist inhalation among the patients with asthma was variable, indicating that bronchial obstruction is not uniformly distributed along the bronchial tree. Measurements of VTGN2 can be easily performed in children from 7 years of age with the method presented. The computerized VTGN2 method facilitates work and saves time for the operator and provides instant test results. VTGN2 appears to be a sensitive indicator of peripheral bronchial obstruction, giving supplemental information to standard spirometry.

Adolescent↗

Gastro-oesophageal reflux and oesophageal dysfunction in children and adolescents with brain damage.

The prevalence of pathological gastro-oesophageal reflux (GOR) and oesophageal dysfunction (OD) was investigated in 32 children, 0.7-19 years of age (mean 11.2 years), with brain damage, mainly severe cerebral palsy and tetraplegia. They underwent 24-h pH monitoring in the distal oesophagus and oesophageal manometry. In addition, radiological examination of the oesophagus, chest radiography, blood counts and blood tests for iron deficiency were carried out. Fifteen (47%) patients had mild pathological acid reflux, 5 (16%) had moderately severe and 5 (16%) severe acid GOR. Seven of 32 (22%) patients had no pathological GOR. Ten patients had abnormal manometry findings and 9 had a pathological radiological oesophagus examination. Three patients had radiographic lung consolidations. Thirteen patients had iron deficiency and 5 were anaemic. Two patients with severe acid reflux have died, presumably from aspiration-induced pneumonia. Findings of OD and GOR are frequent in children with brain damage and are related to significant complications, including fatal course.

Adolescent↗

Evaluation of various models for respiratory inductance plethysmography calibration.

We evaluated one nonlinear and two linear models of the ventilatory system while calibrating the respiratory inductance plethysmograph (RIP) against a pneumotachometer. A calibration method involving voluntary varying rib cage and abdominal contributions to tidal volume in a single body position was utilized. The influence on accuracy of the choice of respiratory phase during calibration was assessed. Both tidal and intratidal volumes were evaluated. Ten adults with no history of respiratory disorders went through RIP calibration and validation in the sitting and supine positions. A linear calibration model, relating lung volume changes from the start of inspiration or expiration to rib cage and abdominal excursions from initiation of respiratory motion, had the best accuracy. The choice of respiratory phase for calibration did not affect accuracy. RIP generally underestimated lung volume at the start of inspiration and overestimated lung volume at the end of inspiration. RIP was more accurate in the supine than the sitting position, probably because of limited spine flexion in the supine position.

Adult↗

Ventilatory pattern during bronchial histamine challenge in asthmatics.

We wanted to investigate whether asthmatic subjects change their ventilatory pattern consistently when forced expiratory volume in one second (FEV1) has declined by at least 20% during bronchial histamine challenge, in order to assess whether respiratory pattern analysis can be used to monitor bronchial obstruction continuously. Histamine challenge was performed twice within a four week period, in eight asthmatic teenagers. Respiratory inductive plethysmography (RIP) was used for respiratory pattern evaluation, whilst the patients breathed on a mouthpiece attached to a pneumo-tachometer (PTM) whilst wearing a noseclip (first histamine challenge), and during natural breathing (second HiCh). End-tidal carbon dioxide tension (PETCO2) was measured on both occasions. During the second histamine challenge, four of the eight patients responded with a 72% (mean) increase in minute ventilation (VE), an 80% increase in mean inspiratory flow (VI), and a 20% decrease in PETCO2. VE and VI were unchanged, or tended to decrease, among the other four patients (ventilatory nonresponders). Neither provocative dose producing a 20% fall in FEV1 (PD20) to histamine nor the magnitude of the fall in FEV1 differed between ventilatory responders and nonresponders. The ventilatory response to inhaled histamine was abolished when breathing through a PTM. Histamine induced bronchospasm is not uniformly reflected in the breathing pattern. Hyperventilation during histamine challenge might be the consequence of vagal airway receptor activation. Respiratory pattern analysis is not a feasible way to monitor bronchial obstruction during histamine challenge.

Adolescent↗