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Biomedical subjects

K M Latimer

Publications and source records attributed to K M Latimer.

At least 19 recordsLinked to original sources
PubMed2000

Mucolytics for bronchiectasis.

BACKGROUND: Bronchiectasis is usually characterised by the production of large quantities of sputum that patients frequently have difficulty in expectorating. Mucolytic agents target hyper-secretion or changed physiochemical properties of sputum to make it easier to clear. One drug, recombinant human DNase, breaks down the DNA that is released at the site of infection by neutrophils. OBJECTIVES: The objective of this review was to assess the effects of ingested or inhaled mucolytics in patients with bronchiectasis. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register, reference lists of relevant articles. We also contacted experts in the field and drug companies. SELECTION CRITERIA: Randomised trials of mucolytic treatment in people with bronchiectasis but not cystic fibrosis. DATA COLLECTION AND ANALYSIS: Data extraction was performed independently by two reviewers. Study authors were contacted for confirmation. MAIN RESULTS: Two trials were included. In one study, compared to placebo, high doses of bromhexine combined with antibiotics eased difficulty in expectoration (weighted mean difference -0.53, 95% confidence interval -0.81 to -0.25 at 16 days). There was also a reduction in sputum production with bromhexine (weighted mean difference -21.5%, 95% confidence interval -38.9 to -4.1 at day 16). There was no difference in forced expiratory volume. In a second study, compared to placebo, recombinant human DNase showed no difference in forced expiratory volume or forced vital capacity. Adverse effects, including influenza-like symptoms, were more common in the group receiving recombinant human DNase. REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate the routine use of mucolytics for bronchiectasis. High doses of bromhexine coupled with antibiotics may help with sputum production and clearance.

Anti-Bacterial Agents↗
PubMed1996

Near-fatal asthma in South Australia: descriptive features and medication use.

BACKGROUND: Self-reported prior morbidity levels and medication use among survivors of a near-fatal asthma attack (NFA) were studied. AIMS: To identify deficiencies in asthma management and opportunities for intervention. METHODS: A hundred and twenty-seven consecutive patients aged 15 years or more presenting with a NFA to accident and emergency departments of teaching hospitals were interviewed. RESULTS: High levels of morbidity due to asthma were reported. Most cases (79%) reported symptoms occurring at least weekly in the three months before their NFA. A mean of 20.8 days was reportedly lost from work, school or other usual daily activity in the 12 months before these events. Regular use of beta agonist as nebuliser solution was reported by 27% of cases, increasing to 34.5% in response to increased symptoms, while 41% reported use of nebulised beta agonist in response to the NFA event. Less than half of all cases (46%) reported using an inhaled corticosteroid on a regular basis. Oral corticosteroids were used by 33% of cases at times of increased symptoms in the preceding 12 months. However, only 7% of cases reported initiating or increasing oral corticosteroids at the time of the NFA. CONCLUSIONS: Despite high levels of prior asthma morbidity, regular preventive inhaled corticosteroid use was not widespread in this series of NFA asthmatics. By comparison, over-reliance on regular beta agonist medication was common. Oral corticosteroids were rarely commenced in response to the NFA.

Administration, Inhalation↗
PubMed1995

Characteristics of near-fatal asthma in childhood.

As part of the South Australian asthma mortality survey, we examined 30 cases of near-fatal asthma attacks in children under 15 years of age who were seen over a 3-year period from May 1988 to June 1991. Subjects presented with asthma and either respiratory arrest, PaCO2 above 50 mm Hg, and/or an altered state of consciousness or inability to speak on presentation at a metropolitan Adelaide teaching hospital. A standardized interview and questionnaire was completed with subjects/parents and medical practitioners. Data were reviewed by the assessment panel which made collective judgments based on predetermined criteria. Seventeen patients (57%) were male, 20% were less than 7 years of age, and the majority (53%) were aged between 12 and 15 years. The majority (83%) had severe asthma and only one case (3.3%) had mild asthma. Half of the subjects were waking every night due to asthma and 79% had significant exercise limitation. A quarter of the subjects had a previous ICU admission and 70% had a hospital admission in the last 12 months. Primary care was carried out by a general practitioner in 57% of cases, and 70% of subjects had a crisis plan. Only 46% of those older than 7 years of age had ever used a peak-flow meter. Eighty percent of subjects or their families had high denial scores, and in 73% of cases psychosocial factors were considered to be significant. Eighty percent of cases experienced acute progressive respiratory distress, and 63% of cases delayed seeking medical care.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Psychiatric and medical features of near fatal asthma.

BACKGROUND: The associations between psychiatric caseness, denial, and self reported measures of handicap and morbidity due to asthma in patients suffering a near fatal attack of asthma have not been fully explored. METHODS: Seventy seven consecutive subjects who presented to Adelaide teaching hospitals with a near fatal attack of asthma were assessed with a validated semi-structured interview following discharge from hospital. RESULTS: 43% of the patients scored > or = 5 on the GHQ-28 questionnaire. There was a positive correlation between GHQ-28 score and limitation to daily activities due to asthma, and between GHQ-28 score and days lost from work, school or usual daily activities, both of which were retained after adjusting for age and sex. Asthma severity did not show a clear association with GHQ-28 score. The asthmatic patients reported high levels of denial, 57% scoring more than 3 out of 5 on the denial scale of the Illness Behaviour Questionnaire. Presentation with a history of progressive respiratory distress was negatively associated with denial score. This persisted after adjustment for age and sex--that is, those with high denial scores were more likely to report presentation as sudden collapse than progressive respiratory distress. CONCLUSIONS: Psychiatric caseness (GHQ score > or = 5) is associated with high levels of morbidity in asthmatic patients who survive a near fatal attack of asthma. High levels of denial in asthmatic subjects may be life threatening. The link between morbidity associated with asthma and psychiatric features, along with other psychosocial issues, warrants further investigation. A broader paradigm than the traditional medical model should be considered when assessing patients with asthma.

Adult↗
PubMed1994

A comparison of asthma deaths and near-fatal asthma attacks in South Australia.

Studies seeking to identify factors predictive of asthma mortality have relied on information obtained from relatives, other close acquaintances, and doctors who cared for the deceased. We wanted to determine whether asthmatics who have suffered a near-fatal asthma attack (NFA) are similar to asthmatics who have died of asthma with respect to important features, because studies of NFA asthmatics may provide a better insight into causes of asthma death. Such studies would avoid the difficulties associated with seeking information secondhand from proxy informants. Two groups were studied: asthmatics who had suffered a near-fatal asthma attack resulting in a visit to the accident and emergency departments of teaching hospitals (n = 154), and asthmatics certified as dying of asthma who, following panel review, were confirmed to have died from this disease (n = 80). For each case in the two groups, an interview questionnaire was administered to a close acquaintance (household or family member) and to the general practitioner. Both groups shared many important characteristics. Similarities related to: frequency of symptoms; frequency of hospital and intensive care unit admissions for asthma; use of asthma crisis plans; compliance with prescribed medications; quality of personal asthma management; and asthma severity. The two groups also showed similar psychiatric profiles, and similar use of asthma medications on a regular basis and with increased symptoms. However, NFA cases tended to be younger, were more likely to be male, and less likely to have concurrent medical conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Near fatal asthma attacks: the reliability of descriptive information collected from close acquaintances.

BACKGROUND: The reliability of information collected from close acquaintances of the deceased in studies on mortality from asthma has not been assessed. As part of a South Australian asthma mortality study, levels of agreement for information obtained directly from cases--that is, cases who had experienced near fatal asthma attacks--were compared with corresponding information concerning these cases obtained independently from close acquaintances. METHODS: The first 51 subjects presenting from the outset of the main study to hospital accident and emergency departments with near fatal asthma attacks were included to gain an early assessment of the reliability of responses. The level of agreement between self reported information and that obtained from close acquaintances was compared by means of a kappa statistic or intraclass correlation coefficient, depending on the measurement scale. Both score one for complete agreement and zero when there is no agreement. RESULTS: High levels of agreement were found for questions relating to use of hospital services, with agreement levels ranging from 0.92 for visits in the past month to accident and emergency departments, to 0.86 for prior hospital admissions and 0.78 for prior need for assisted ventilation. Levels of agreement for drug treatment ranged from 1.00 for use of beta agonists to 0.64 for corticosteroid use, and to a low 0.24 for use of sodium cromoglycate. There was moderate agreement for histories of regular use of over the counter medications without a medical consultation (0.57). Psychiatric characteristics showed moderate levels of agreement, with values of 0.44 for personal history of psychiatric consultations and 0.50 for denial score. Agreement scores were 0.66 for doctor visits in the past month, 0.66 for limitations in daily activities, 0.76 for loss of work days in the past month, 0.59 for severity of asthma, and 0.55 for frequency of asthma attacks in the past month. Poorer agreement scores were found for trends in asthma symptoms (0.21) and frequency of symptoms during the past three years (0.12). Sleep disturbance was also associated with a low agreement score (0.25). CONCLUSIONS: The more visible the asthma manifestation, and the more recent the period to which it applies, the more reliable is the information provided by close acquaintances. These factors need to be taken into account when using information from close acquaintances in asthma mortality studies.

Adolescent↗
PubMed1992

Accuracy of asthma statistics from death certificates in South Australia.

OBJECTIVE: To assess the accuracy of asthma statistics from death certificates in South Australia. DESIGN: Comparison of death certificate coding with expert panel assessments of causes of death after interviews with certifying doctors, regular medical practitioners and close acquaintances of the deceased. SUBJECTS: 261 subjects for whom the term "asthma", "asthmatic" or "asthmaticus" was recorded in Part I or Part II of death certificates lodged in the 24-month period from May 1988. MAIN OUTCOME MEASURES: Sensitivity, specificity and predictive value of death certificate coding, with expert panel assessments as the reference standard. RESULTS: About 95% of deaths assessed as definitely due to asthma were so coded from death certificates, but only 69% of deaths assessed by the panel as not due to asthma were coded to a "non-asthmatic" cause. Of the 129 deaths coded to asthma, the percentage assessed as definitely or likely to be due to asthma was 56%. For ages under 65 years, this figure was 84% compared with only 38% for older subjects. CONCLUSION: The accuracy of death certificate data on asthma for the age group 65 years and over would be too low at present for most epidemiological purposes.

Abstracting and Indexing↗
PubMed1991

Longitudinal study of near fatal asthma.

The effect of careful follow-up and treatment modification for 45 patients with an admission for NFA has been studied. In 24 of 45, inciting events were recognized. BDP was used by 14 patients pre-NFA. In the mean follow-up of 863 days, there have been no deaths and seven patients have been readmitted with asthma. Six of the 45 patients have attained normal FEV1 and PC20H. Blunted perception of breathlessness, change in VAS ratio/change in FEV1, was found when first measured, but normalized to be no different than that of other asthmatic subjects as airway responsiveness became milder. The CO2 ventilatory responses did not differentiate individual NFA patients from non-NFA asthmatic or normal subjects. Comparison of the NFA cohort with the 1985 asthma admission cohort showed that an asthma admission within the last five years was a risk factor for a NFA episode.

Adult↗
PubMed1991

Lack of effect of 4 weeks of oral H1 antagonist on bronchial responsiveness.

Ten patients with stable chronic asthma completed a randomized double-blind placebo controlled crossover study examining the effect of 120mg terfenadine twice daily for 4 weeks on bronchial responsiveness. Bronchial responsiveness was measured by methacholine inhalation tests performed by the tidal breathing technique at 0, 2 and 4 weeks of active and placebo treatment periods separated by a one week washout period. There were no significant differences in mean baseline forced expired volume in 1 sec (FEV1) for placebo and terfenadine treatments (p greater than 0.05) and there were no differences between geometric mean provocative concentrations of methacholine to cause a 20% fall in FEV1 (PC20M) at 2 and 4 weeks of terfenadine (0.89 and 0.99 mg.ml.1) from placebo (0.94 and 0.84 mg.ml.1) (p greater than 0.05). Examination of individual PC20M values during terfenadine treatment showed that 5 patients had PC20M's outside their 95% confidence interval; 2 increased both 2 and 4 week values, 1 increased one value and 2 decreased one value each. It is concluded that terfenadine does not produce clinically significant changes in stable asthmatics.

Administration, Oral↗
PubMed1990

Bronchial hyperresponsiveness in two populations of South Australian rural schoolchildren.

This report describes the cross-sectional analyses of the results obtained from the first year of a longitudinal study designed to investigate the natural history of bronchial hyperresponsiveness in association with reported respiratory symptoms in children attending the Burra and Kingston Community Schools. Bronchial hyperresponsiveness to methacholine was measured using a modified Yan technique. Prevalence rates of respiratory symptoms were obtained using the Tasmanian Asthma Foundation Questionnaire. Considerable overlap of reported symptoms of asthma and/or wheezy breathing and bronchitis and/or loose and productive cough was observed suggesting that a clear distinction between such symptoms in childhood may not be possible. Analyses of data showed the prevalence of reactive airways in children to be 21.3% in Burra and 22.0% in Kingston. These values were the same as results obtained from an earlier pilot study in Burra and similar to results from Wagga Wagga (19.6%) and Auckland (20.1%) but higher than from Belmont (15.5%) and Villawood (15.3%). Increased bronchial hyperresponsiveness was associated with the reporting of symptoms of asthma and/or wheezy breathing (odds ratio, 5.04; 95% confidence interval, 2.18-11.74) and bronchitis and/or loose and productive cough (odds ratio, 2.28; 95% confidence interval, 1.02-5.13), at any time in the child's life. Of children with no reported symptoms 10% also had demonstrable bronchial hyperresponsiveness.

Asthma↗
PubMed1990

Bronchoconstriction of the asthmatic airway by inhaled and ingested propranolol.

Responsiveness to inhaled histamine and DL propranolol hydrochloride was measured in 31 adult asthmatics and compared with bronchoconstriction provoked by acute oral propranolol dosing (max 160 mg). Twelve asthmatics developed greater than or equal to 15% reduction in the forced expired volume in 1 s (FEV1), 2 h after less than or equal to 100 mg oral propranolol; cardiac beta-adrenoceptor blockade was confirmed by cycle exercise tests in the 19 without airway response. The provocative inhaled dose of each aerosol causing a 20% fall in FEV1 (PC20) was lower, histamine 0.43 mg.ml-1, propranolol 3.12 mg.ml-1, in the 12 with a positive oral test compared with the 19 with a negative test, PC20 histamine 1.65 mg.ml-1, PC20 propranolol 16.2 mg.ml-1 (P less than 0.001 for both aerosols). A correlation was demonstrated between the PC20 values for asthmatics with a negative oral test (r = 0.72, P less than 0.001, n = 19) but not for the remainder (r = 0.14, P greater than 0.05, n = 12). Plasma propranolol concentrations (CL, ng.ml-1) after the final oral dose did not correlate with the % delta FEV1 (26.3) (r = -0.28) when an airway response was provoked or with the reduction in exercise tachycardia (25.9%) (r = 0.31) when no bronchoconstriction occurred. CL exceeded the limit of detection after the final inhaled propranolol dose (7.5 ng.ml-1) and was weakly related to the PC20 propranolol value (r = 0.53, P = 0.01, n = 27). The prevalence of a positive oral challenge was low in this group (39%).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1990

The effect of inhaled fenoterol and ipratropium bromide on propranolol induced bronchoconstriction in the asthmatic airways.

1. The provocative dose of inhaled propranolol, (PC20P, mg/mL) needed to induce a 20% reduction in the forced expired volume in 1 s (FEV1, L) was determined for 15 adult asthmatics following randomized pre-treatment with placebo, ipratropium bromide (40, 160 micrograms) and fenoterol (200, 800 micrograms) aerosols using a double-blind protocol. 2. Fenoterol 200 micrograms, 800 micrograms increased the baseline FEV1 0.28 +/- 0.16, 0.32 +/- 0.16 L (P = 0.04, P = 0.008 respectively). Fenoterol 800 micrograms moved the PC20 P rightwards from placebo geometric mean 10.95, 95% Confidence Intervals (95% CI) 4.43-27.22 mg/mL to mean 20.41, 95% CI 10.13 to 40.64 mg/mL (P = 0.01). Fenoterol 200 micrograms was not protective; mean PC20 16.22, 95% CI 7.83-34.35 mg/mL (P = 0.08). Neither 40 or 160 micrograms ipratropium changed the FEV1 or PC20P values compared with placebo; increase in FEV1 0.15 +/- 0.27 L (P = 0.22), 0.24 +/- 0.12 L (P = 0.14) and geometric mean PC20P 16.59 +/- 0.57 mg/mL, 95% CI 8.01-34.51 mg/mL (P = 0.90), 15.58 +/- 0.66 mg/mL, 95% CI 6.72-36.05 mg/mL (P = 0.34) respectively after ipratropium treatments. 3. Bronchoconstriction induced by inhaled propranolol (P) appears to be only weakly antagonized by inhaled beta-agonist and not reduced by antimuscarinic anticholinergic aerosol. This finding argues against the activation of a cholinergic reflex to explain propranolol induced bronchoconstriction (PIB).

Administration, Inhalation↗
PubMed1989

A comparative bronchodilator study of salbutamol and salbutamol sulphate that were administered by metered-dose inhalers.

Twenty-one patients with mild-to-moderately-severe asthma participated in a placebo-controlled, double-blind, cross-over, randomized bronchodilator study of 200 micrograms of salbutamol (Glaxo) and 200 micrograms of salbutamol in the form of salbutamol sulphate (Riker; 50-microL and 25-microL valves) that were administered by metered-dose inhalers. The mean baseline forced expired volumes in one second (FEV1) were similar for the four separate study days. The three active treatments caused a significantly-greater FEV1 response than did placebo for four hours (P less than 0.05) and no difference was found between the treatments (P greater than 0.05). The power of the study was 75% with a clinically-significant difference in the FEV1 response of 25%. The administration of 200 micrograms of salbutamol (Glaxo) caused the same FEV1 response as did that of 400 micrograms of salbutamol at the end of that study day (P greater than 0.05), but both 200-micrograms doses of salbutamol sulphate (Riker) caused a smaller FEV1 response than did the 400 micrograms of salbutamol sulphate (P less than 0.05). These observations indicate that no clinically-significant difference occurs between the bronchodilator effects of salbutamol and those of salbutamol sulphate which is administered as 200 micrograms of salbutamol equivalent, with different propellant mixtures, dispersal agents and valvular systems.

Adult↗
PubMed1988

Biochemical studies of N-methyltransferase in human and guinea-pig lung: no apparent role in the pathogenesis of asthma.

1. N-Methyltransferase activity was measured in surgical specimens of human lung using phenylethanolamine as substrate. Thirty-three male and seven female patients, age range 19-78 (median 62.5) years were studied. The activity in lung homogenates was 0.59 x 10(-6) units/mg of protein (SEM 0.03, n = 40), with a range of 0.16-1.16 x 10(-6) units/mg of protein. There was no difference (P = 0.97) in activity between males and females. 2. Non-specific N-methyltransferase activity was estimated in 17 of the surgical specimens using beta-phenylethylamine as substrate. This activity was 38.9% (SEM 5.3) of that with phenylethanolamine. Comparative studies with rabbit lung, which has a well-characterized non-specific N-methyltransferase, showed significant differences in substrate specificity between the two species. 3. The apparent Km and Vmax for phenylethanolamine in seven human lung homogenates was 22.0 (SEM 4.6).mmol/l and 1.82 x 10(-6) units/mg of protein (SEM 0.36). The noradrenaline N-methyltransferase (NMT; EC 2.1.1.28) inhibitors SKF 64139-A and LY 134046 did not inhibit this activity up to a concentration of 100 mumol/l. This activity was inhibited 51.4% (SEM 8.6, n = 6) by 100 mumol/l S-adenosyl-L-homocysteine. Immunohistochemistry did not reveal immunoreactive NMT in human lung sections. 4. Comparative studies with guinea-pig lung homogenates demonstrated non-specific N-methyltransferase activity in this species which is similar to the human lung.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Hydroxyphenethylamine↗
PubMed1988

The effect of trifluoperazine on bronchial responsiveness in asthma.

1. The protective effects of oral trifluoperazine (TFP) (7 mg) against standardized methacholine and histamine inhalation tests (MIT and HIT) were examined 2 and 22 h post-treatment in eight stable asthmatics using a randomized double-blind protocol. 2. A preliminary study tested whether a preceding MIT influenced the result of a subsequent HIT. 3. The mean baseline forced expiratory volumes in 1 s (FEV1) were similar prior to placebo and TFP. The mean FEV1 values 2 h after ingestion of placebo or TFP were not different from the baseline values. 4. TFP did not alter bronchial responsiveness to inhaled methacholine or histamine 2 h post-ingestion, but at 22 h the PC20 methacholine was greater than placebo, while PC20 histamine did not change. This change in methacholine responsiveness was not clinically significant. 5. There was a correlation between geometric mean provocative concentration of histamine to cause 20% fall in FEV (PC20H) for HIT performed in isolation ('separate day') and for HIT performed after MIT ('same day'). 6. The effect of inhaled TFP (10 mg/ml, nebulized for 5 min) was examined single-blind and placebo-controlled in a separate group of six stable asthmatics. 7. Inhaled TFP had a bronchoconstrictor effect in all six asthmatics. The mean fall in FEV1 was 36.4% after inhaled TFP and 2.1% after saline. 8. In the asthmatics studied, ingested TFP exhibited a weak anticholinergic effect 22 h post-treatment, but a brisk spontaneously self reverting bronchoconstrictor response was invariably seen when TFP was inhaled.

Adolescent↗
PubMed1986

Airway responses to hyperventilation of cold dry air: duration of protection by cromolyn sodium.

The magnitude and duration of the inhibitory effect of three doses of cromolyn sodium on the airway response to hyperventilation of cold dry air was examined in a double-blind, randomized controlled trial. Eight subjects with well controlled asthma were studied. On 4 separate days, doses of either 2 mg, 10 mg, 20 mg, or placebo were administered by metered-dose inhaler. Twenty minutes, 2 hours, and 4 hours after each medication, airway responsiveness to isocapnic hyperventilation of cold dry air was measured by use of a standardized dose-response method. At 20 minutes, all three doses inhibited bronchoconstriction, and there was no evidence of any difference in the magnitude of the inhibition between the doses. All three doses progressively provided less protection with time. By 2 hours, the inhibition induced by 2 mg was no longer different from placebo, and by 4 hours, only 20 mg still provided significant protection. The results demonstrate that, although the initial magnitude of inhibition may not be different between 2 mg and 20 mg, the rate at which the protective effect wears off is dose related.

Adolescent↗
PubMed1985

Effect of beclomethasone dipropionate on bronchial responsiveness to histamine in controlled nonsteroid-dependent asthma.

We investigated the possibility that corticosteroids can reduce bronchial responsiveness to histamine by mechanisms other than change in airway caliber. Ten adult asthmatic subjects were selected because their symptoms were controlled by bronchodilators alone, they had no recent respiratory infection or allergen exposure that might have temporarily altered responsiveness, their spirometry was more than 70% predicted, and they had a range of histamine bronchial hyperresponsiveness. They received, in random order and double-blind manner, beclomethasone dipropionate (400 micrograms daily) or placebo for 4 wk and then, after a 2-week washout period, they crossed over to the other treatment for 4 wk. Treatment with beclomethasone induced a small but significant reduction in bronchial responsiveness to histamine (p = 0.014). Although the improvement was too small to be considered of clinical significance, its importance lies in the mechanisms by which it was produced. Part of the improvement was related to improvement in airway caliber, but, even when the data was adjusted for this, there was still a significant difference between beclomethasone and placebo treatment (p = 0.018). The results suggest that regular treatment with corticosteroids can alter bronchial responsiveness through mechanisms other than change in airway caliber.

Adult↗