Asthma Abstracts

Asthma Abstracts
by Dr. Gary Farr on 12 February 2002

Part 1

Asthma

Rate of Asthma Doubles

July 8, 2000
British Medical Journal 2000;321:88-92

British researchers report that in the last 20 years allergy-induced asthma has doubled in the adult population. They found no connection between smoking and this doubling of asthma cases since, during the same period, the rate of smoking had declined by 50 percent.

As a result of this trend, between 1980 and 1990 prescriptions for inhaled steroids to treat asthma increased by over 600% .

Longitudinal growth in infants and young children treated with budesonide inhalation suspension for persistent asthma.

Skoner DP, Szefler SJ, Welch M, Walton-Bowen K, Cruz-Rivera M, Smith JA.
J Allergy Clin Immunol 2000 Jan;105(2 Pt 1):259-68.

The results of this study show that treatment with inhaled corticosteroids (budesonide. suspension) negatively affects growth in young asthmatic children. The study presents the results of 3 trials conducted on 670 asthmatic children aged 6 months to 8 years, followed for a year. In the first trial, children were randomly assigned to receive either budesonide inhaled suspension or conventional treatment without steroids; in the other 2 trials, children were randomly assigned to either budesonide inhaled suspension or to conventional treatment with steroids. Children in the first trial who received budesonide manifested significant height reduction and reduced growth velocity, compared to those who did not use inhaled corticosteroids, confirming the results of other studies indicating that inhaled glucocorticosteroids may interfere with growth in children.

Frequent paracetamol use and asthma in adults.

Shaheen SO, et al.
Thorax 2000 Apr;55(4):266-270.

The results of this study show that users of paracetamol have a significantly increased risk of developing asthma and of having more severe disease, compared to nonusers. Paracetamol has been shown in animals to deplete the lung of the natural anti-oxidant glutathione, and may therefore render the lung more susceptible to inflammation. The researchers investigated a possible association between use of this drug and asthma by evaluating paracetamol intake in 664 asthmatic patients and 910 healthy controls. Use of paracetamol was found to be significantly associated with increased risk of asthma. In particular, individuals who took the drug infrequently (less than monthly) had only a 6% increased risk of asthma. The risk, however, increased by 22%, 80%, and 240% times in monthly, weekly, and daily users, respectively, compared to nonusers. The relation between paracetamol intake and asthma was particularly strong in patients with severe disease. Asthmatic patients who took paracetamol had more severe disease, compared to those who did not use it. These results are of particular relevance, since approximately 20% of asthmatic patients in this study were taking paracetamol on a daily or weekly basis. A reduction of the intake of this drug may therefore translate in a significant reduction in asthma morbidity.

Preferential pulmonary retention of (S)-albuterol after inhalation of racemic albuterol.

Dhand R, et al.
Am J Respir Crit Care Med 1999 Oct;160(4):1136-41

This study shows that racemic albuterol, used to relieve bronchocostriction in asthmatic patients, consists of a (R)-enantiomer which induces bronchodilation, and a (S)-enantiomer which causes bronchoconstriction. The metabolism of the two enantiomers differs; the (R)-enantiomer is metabolized faster while the (S)-enantiomer accumulates in the lungs. The preferential retention in the lungs of the (S)-enantiomer could explain the increased airway obstruction that can be seen in patients on long-term treatment with albuterol.

Drug use and pulmonary death rates in increasingly symptomatic asthma patients in the UK.

Meier CR; Jick H.
Thorax, 52(7):612-7 1997 Jul

This study shows that asthma patients receiving ipratropium bromide and theophylline have a 80% and 3-fold increased risk of death from respiratory causes, respectively, compared to those taking salmeterol. All three drug are regularly used for patients with asthma of increasing severity.

The effect of drug therapy on long-term outcome of childhood asthma: a possible preview of the international guidelines.

K╫nig P; Shaffer J.
J Allergy Clin Immunol, 98(6 Pt 1):1103-11 1996 Dec

This retrospective study shows that "as needed" use of bronchodilators does not improve the long-term prognosis of childhood asthma.

Adverse effects of inhaled corticosteroids.

Hanania NA; Chapman KR; Kesten S.
Am J Med, 98(2):196-208 1995 Feb

This study shows that the trend of prescribing corticosteroids as anti-inflammatory drugs for adult asthma to a growing number of patients, in larger doses and for longer periods of time, has been associated with an increased rate of potentially serious systemic adverse reactions such as adrenal suppression, osteoporosis, cataract, stunted growth in children, altered metabolism, and behavioral abnormalities.

Adverse effects of medications for rhinitis.

Milgrom H; Bender B.
Ann Allergy Asthma Immunol, 78(5):439-44; 1997 May

This article discusses some of the side effects associated with symptomatic treatment of rhinitis such as cardiac arrhythmias, sedation, psychosis, impaired learning and memory. These complications have been reported after use of antihistamines, decongestants, anticholinergic agents, and corticosteroids, used in combination or alone.

Introduction: risk management in asthma and allergic diseases.

Du Buske LM .
J Allergy Clin Immunol, 98(6 Pt 3):S289-90 1996 Dec

This article warns physicians to carefully evaluate the risks and benefits associated with the symptomatic treatment of allergic diseases such as rhinitis, asthma, and urticaria. First-generation antihistamines, for example, are of unproven efficacy and cause potentially dangerous sedation and impairment in cognitive performances. Second-generation antihistamines have been shown to interact with some antibiotics and antifungal agents and potentially causing life-threatening cardiac arrhythmias.

Inhaled steroids and the risk of hospitalization for asthma.

Donahue JG; et al.
JAMA, 277(11):887-91 1997 Mar 19

This study shows that while inhaled steroids and cromolyn reduce the risk of hospitalization for asthma, increasing use of beta-agonists is associated with increasing risk of hospitalization.

The use of children's medical records to predict the risk of asthma attack.

Neville RG; Bryce FP; Clark RA; Crombie IK.
Scott Med J, 40(5):138-40 1995 Oct

This study evaluated potential risk factors for the development of an asthma attack. It was shown that 27% of children who received antibiotics for a respiratory infection subsequently had an asthma attack.

Actual use of inhaled corticosteroids and risk of hospitalisation: a case-control study.

van Ganse E; Hubloue I; Vincken W; Leufkens HG; Gregoire J; Ernst P
Eur J Clin Pharmacol, 51(6):449-54 1997

This study shows that asthmatic patients who rely significantly on beta 2-agonists and use less than optimal doses of inhaled corticosteroids have an over 5-fold increased risk of being hospitalized for asthma.

Changing patterns of asthma mortality. Identifying target populations at high risk.
Weiss KB; Wagener DK.
JAMA, 264(13):1683-7 1990 Oct 3

This study shows that asthma mortality rates in the 1970s declined by 7.8% per year, while in the 1980s they increased by 6.2% per year. These differences cannot be attributed to changes in the definition of the disease nor to increased detection of asthma cases..

Regular inhaled beta-agonist treatment in bronchial asthma

Sears MR et al.
Lancet, 336(8728):1391-6 1990 Dec 8

This double-blind placebo controlled study conducted on 89 asthmatic patients shows that the majority of patients randomized to fenoterol experienced worsening of asthma compared to those receiving placebo. The authors concluded that regular use of beta-agonists may contribute to the worldwide increase in asthma morbidity.

Case-control study of prescribed fenoterol and death from asthma in New Zealand,

1977-81.
Pearce N; et al.
Thorax, 45(3):170-5 1990 Mar

This case control study shows that asthmatic patients taking fenoterol have a twofold increased risk of death compared to those not taking the drug. In patients taking 3 or more categories of asthma drugs the risk increased by three times; in patients on oral corticosteroids the risk increased by approximately six times, and in those with the most severe asthma (treated with oral corticosteroids and with a history of hospital admission for asthma attack in the previous year) the risk was increased by almost ten times.

Prescribed fenoterol and death from asthma in New Zealand, 1981-7: a further case-control study.

Grainger J; et al.
Thorax, 46(2):105-11 1991 Feb

This study shows that asthmatic patients aged 5 to 45 years who took inhaled fenoterol had an over twofold increased asthma mortality, compared to nonusers.

The use of beta-agonists and the risk of death and near death from asthma.

Spitzer WO, et al.
N Engl J Med 1992 Feb 20;326(8):501-6

This study shows that asthmatic patients taking regularly beta-agonists via a metered-dose inhaler have a 2.6-fold increased risk of death from asthma compared to non-users. The risk associated with use of the beta-agonist fenoterol was increased by 5.4-times, and that associated with use of the beta-agonist albuterol was increased by 2.4-times.

End of the New Zealand asthma mortality epidemic.

Pearce N; Beasley R; Crane J; Burgess C; Jackson R.
Lancet, 345(8941):41-4 1995 Jan 7

This study reports on the epidemic of asthma deaths that started in 1976 in New Zealand, concomitantly with the introduction of the asthma drug fenoterol. After a case-control study revealed in 1989 that the drug caused an over twofold increase in mortality, death rates, for the first time after more than a decade, fell by half and remained low in the following years.

Asthma medications and disease exacerbations: an epidemiological study as a method for asthma surveillance.

Van Ganse E et al.
Eur Respir J, 8(11):1856-60 1995 Nov

This study, conducted on a sample of 680 asthmatic patients, shows that users of fenoterol and oral xanthines have a higher risk of asthma worsening, compared to nonusers.

Sudden death from asthma in 108 children and young adults.

Tough SC; Green FH; Paul JE; Wigle DT; Butt JC. J Asthma, 33(3):179-88 1996

This study evaluated factors that may be associated with increased risk of death in a sample of 108 children or young adults who died of acute asthma. Adrenal suppression was found in 18.7% of cases, indicating that complications derived from use of corticosteroids may, in some cases, contribute to death in this population.

Bronchodilators and acute cardiac death.

Suissa S; Hemmelgarn B; Blais L; Ernst P.
Am J Respir Crit Care Med, 154(6 Pt 1):1598-602 1996 Dec

This study, conducted on a sample population of 12,301 asthmatic patients, shows that those taking theophylline and beta-agonists have, respectively, a 2.7- and 2.4-fold increased risk of death from cardiovascular complications compared to nonusers. The association with beta-agonists was found for the preparations administered orally or by nebulizer.

Treatment of allergic rhinitis: effects of allergic rhinitis and antihistamines on performance.

Storms WW. A
Allergy Asthma Proc, 18(2):59-61 1997 Mar-Apr

This study reviews some of the side effects associated with antihistamines, the most commonly used class of drugs for allergic rhinitis, which include sleepiness, impairment in cognitive performances, impaired driving and working performances, and reduced motor and verbal activity. Children's learning skills and performances may be negatively affected by these drugs.

Management of steroid-dependent asthma with methotrexate: a meta-analysis of randomized clinical trials.

Aaron SD, Dales RE, Pham B.
Respir Med 1998 Aug;92(8):1059-65

This study evaluated 12 double-blind, placebo controlled trials assessing the effects of low-dose methotrexate in reducing corticosteroids dosage in patients with severe asthma. Methotrexate was associated with an 18% reduction in corticosteroids use, compared to placebo. However, the drug caused a higher rate of gastrointestinal complications and of liver toxicity. Furthermore, among the 159 patients randomized to methotrexate there were three potentially fatal complications (two pneumonias and one severe liver dysfunction), versus none in patients receiving placebo.
Part 2
Benefits and complications of troleandomycin (TAO) in young children with steroid-dependent asthma.

Flotte TR; Loughlin GM.
Pediatr Pulmonol, 10(3):178-82 1991

This study shows that use of troleandomycin in children with severe, steroid-dependent asthma, reduces steroid requirements and hospitalization rates, but increases the rate of steroid-dependent complications. In particular, the rate of cataracts increased from 11% to 33% and the rate of hypercholesterolemia increased from 22% to 78%.

Increased morbidity and mortality related to asthma among asthmatic patients who use major tranquillisers

Joseph, K S. et al.
BMJ 1996;312:79-81 (13 January)

This study shows that asthmatic patients using major tranquillisers have an over three-fold increased risk of death or near death from asthma, compared to nonusers. The risk seems to be particularly high in patients who recently discontinued the use of tranquillisers.

Relation of infant diet to childhood health: seven year follow up of cohort of children in Dundee infant feeding study

Wilson AC. Et al.
BMJ 1998;316:21-25 (3 January)

This study, conducted on 545 infants followed up for approximately 7 years, shows that the incidence of respiratory illnesses was greatly reduced in infants who were exclusively breast fed for at least 15 weeks (17%) compared to those who were partially breast-fed or bottle fed (31% and 32% respectively). Introduction of solid foods before 15 weeks was associated with increased risk of wheeze during childhood (21% vs. 10%), and with increased percentage of body fat and weight in childhood. Bottle feeding was associated with a significant increase in systolic blood pressure compared to breast feeding (mean systolic blood pressure 94.2 mm Hg vs. 90.7 mm Hg). The results of this study show that breast feeding and avoidance of solid foods during the infants' first 15 weeks can have a great impact on the health of children and later, adults.

US in the dark on doubling in asthma death rates. News

Roberts, J.
BMJ 1996;312:1246 (18 May)

This article reports on a study from the Centers for Disease Control and Prevention (CDC) revealing that in the U.S., rates of death due to asthma more than doubled in the period from 1980 to 1993. This increase in death occurred especially among African American, who, in 1993, were 6 times more likely to die of asthma in the first 4 years of life and from the age of 15 to that of 24, compared to whites. Since asthma mortality rates have been used as a marker of effective health care delivery, these data seem to indicate problems in the health care system.

Controversies involving inhaled beta-agonists and inhaled corticosteroids in the treatment of asthma.

Fahy JV, Boushey HA
Clin Chest Med 1995 Dec;16(4):715-33

This article reviews some of the controversies surrounding the use of
inhaled beta-agonists and inhaled corticosteroids in asthma patients. While it is well known that excessive use of beta-agonists increases the risk of asthmatic death, it is yet to be defined whether regular use may be associated with worsening of asthma control. As for inhaled corticosteroids, the issue is whether the benefits derived by their use outweigh the risks of long-term toxicity such as osteoporosis, cataracts and stunted growth, and whether treatment benefits are only short-lasting.

Case-control study of salmeterol and near-fatal attacks of asthma.

Williams C, et al.
Thorax 1998 Jan;53(1):7-13

This case-control study shows that asthmatic patients receiving the beta agonist salmeterol have a 2.3-fold increased risk of near-fatal asthma attacks compared to nonusers. When the analysis was restricted to severe cases only, the risk was increased by 40%. The risk of near fatal asthma attacks was associated with the mode of delivery of the drug. In particular, patients receiving a beta agonist by metered dose inhaler did not have an increased risk, while those who received it by nebulizer had an almost 4-fold increased rate of near fatal asthma attacks. Asthmatic patients receiving oral theophylline were 2.5-times more likely to have a near fatal asthma attack compared to nonusers.

The association between beta-agonist use and death from asthma. A meta-analytic integration of case-control studies.

Mullen M, Mullen B, Carey M
JAMA 1993 Oct 20;270(15):1842-5

This study analyzed 6 case-control studies investigating the relationship between use of beta agonists and death from asthma. The results of the analysis revealed that use of beta agonists by nebulizer, but not by metered-dose inhaler, is significantly associated with increased risk of death. The risk is particularly elevated in adults compared to adolescents.

Prescribed drug therapy and near-fatal asthma attacks.

Burgess C, et al.
Eur Respir J 1994 Mar;7(3):498-503

This study shows that the rate of near fatal asthma attacks is doubled in patients receiving fenoterol versus nonusers. Use of theophylline was associated with a 90% increased risk of near fatal asthma attacks.

Asthma medications and disease exacerbations: an epidemiological study as a method for asthma surveillance.

Van Ganse E, et al.
Eur Respir J 1995 Nov;8(11):1856-60

This study, conducted on a sample group of 680 asthmatic patients, shows that use of oral xanthines and inhaled fenoterol is associated with an increased likelihood of asthma exacerbation.

Long-and short-acting beta 2-adrenergic agonists. Effects on airway function in patients with asthma.

Busse WW.
Arch Intern Med 1996 Jul 22;156(14):1514-20

This article reports that use of beta agonist bronchodilators was first shown to be associated with increased asthma morbidity and mortality in the 1960s in U.K. and in the 1970s in New Zealand. However, to this day, controversies about their safety and efficacy still exist, and there are concerns that long-term use of this class of drug may be associated with loss of asthma control in some patients.

The beta-agonist controversy.

Taylor DR, Sears MR, Cockcroft DW
Med Clin North Am 1996 Jul;80(4):719-48

This article emphasizes that treatment with short-acting beta agonists is strongly associated with increased death from asthma. Furthermore, the evidence that long-term beta agonist therapy improves symptoms and lung functionality in asthmatic patients is meager, while adverse events from treatment are well documented. Long-term use of short-acting beta agonists as also been associated with deterioration of asthma control. Whether also long-acting beta agonists produce the same effect is not yet clearly defined.

Regular inhaled beta agonist in asthma: effects on exacerbations and lung function.

Taylor DR, et al.
Thorax 1993 Feb;48(2):134-8

This double-blind placebo controlled crossover study shows that asthmatic patients who use regularly the beta agonist fenoterol have higher rates of asthma attacks, significant worsening of lung function and increased airway responsiveness compared to patients who take the drug "as needed".

Hospital treatment of asthma: lack of benefit from theophylline given in addition to nebulized albuterol and intravenously administered corticosteroid.

DiGiulio GA, Kercsmar CM, Krug SE, Alpert SE, Marx CM
J Pediatr 1993 Mar;122(3):464-9

This double-blind, placebo controlled study shows that the addiction of theophylline to a drug regimen consisting of nebulized albuterol and intravenous steroids in children hospitalized for asthma may not be justified since it is not associated with improvement of asthma symptoms and lung functionality nor with reduced length of hospitalization.

Aminophylline toxicity--how many hospital asthma deaths does it cause?

Eason J, Markowe HL
Respir Med 1989 May;83(3):219-26

This study shows that 21% of patients who died from asthma attacks might have had toxic theophylline levels in their blood, compared to only 7% of those who were hospitalized for acute asthma but survived the attack.
It is possible that theophylline toxicity may contribute to death from asthma in a significant proportion of patients.

Life-threatening events after theophylline overdose: a 10-year prospective analysis.

Shannon M
Arch Intern Med 1999 May 10;159(9):989-94

This study shows that in spite of a decline in use of theophyllines in the treatment of asthma, cases of fatal or near fatal intoxication are still occurring.
Three hundred fifty-six patients with theophylline toxicity were followed up prospectively. Cardiac arrhythmias occurred in 21%, seizures in 8%, and death in 4.2% (15) of patients. About 75% of patients who died were chronically overmedicated. The authors conclude that theophylline toxicity is associated with substantial morbidity and mortality, and its use should be reduced to a minimal.

Risk factors for death from asthma, chronic obstructive pulmonary disease & cardiovascular disease after a hospital admission for asthma.

Guite HF, Dundas R, Burney PG
Thorax 1999 Apr;54(4):301-7

This study shows that patients treated with ipratropium bromide, an anticholinergic agent used as bronchodilator in maintenance therapy of asthmatic patients, are four times more likely to die from asthma compared to nonusers. Asthmatic patients taking pratropium bromide have also an almost 8-fold increased risk of death from chronic obstructive pulmonary disease, and a 3.5-fold increased risk of death from cardiovascular diseases.

Near-death asthmatic reaction induced by disodium cromoglycate.

Katayama H, et al.
Intern Med 1996 Dec;35(12):976-8

This study reports on the case of a patient who suffered from a near death asthmatic attack after inhaling disodium cromoglycate (DSCG). This article emphasizes a possible association between DSCG and fatal asthma.

Risk of non-fatal cardiac failure and ischaemic heart disease with long acting beta 2 agonists.

Martin RM, Dunn NR, Freemantle SN, Mann RD
Thorax 1998 Jul;53(7):558-62

This study evaluated the risk of non-fatal cardiac failure and ischemic heart disease in over 12,000 asthmatic patients taking nedocromil, over 15,000 patients taking the beta agonist salmeterol, and approximately 8,000 patients taking the beta agonist bambuterol. Patients receiving bambuterol and salmeterol had a 3.4-fold and 10% increased risk of non fatal cardiac failure, respectively, compared to patients taking nedocromil. The risk of non fatal ischemic heart disease was increased by 23% and 7% in patients taking bambuterol and salmeterol, respectively, compared to those receiving nedocromil. Asthmatic patients who just started therapy with bambuterol had a 4-fold increased risk of ischemic heart disease in the first month of treatment.

Aminophylline in acute asthma.

Olson LG
Aust N Z J Med 1987 Apr;17(2):263-6

This article reports on the results of several trials showing that the drug theophylline used in patients treated with high doses of beta agonists adds no benefits in terms of reduced morbidity or mortality. Since, on the other hand, it is difficult to keep theophylline serum concentration within safe limits, and, furthermore, the effects of toxic levels can be very serious, the author recommends that the drug be used only in restricted circumstances and in limited amounts.

Use of inhaled corticosteroids and the risk of cataracts.

Cumming RG ; Mitchell P ; Leeder SR
N Engl J Med, 337(1):8-14 1997 Jul 3

This study, conducted on 3,654 individuals aged 49 years and older, shows that current or previous users of inhaled corticosteroids have twice the risk of posterior subcapsular cataracts -the most serious type of cataract- compared to nonusers. The risk of cataracts increases with increasing use of inhaled corticosteroids, and 27% of individuals who took the drug for the longest time developed cataracts, more than five times the usual. This is the first study to reveal that the association between steroids and cataracts is not restricted to systemic and ocular corticosteroids but includes the inhaled forms.

Inhaled corticosteroids and cataract: prevalence, prevention & management.

Cumming RG, Mitchell P
Drug Saf 1999 Jan;20(1):77-84

This article emphasizes that the association between inhaled corticosteroids and the risk of developing the most serious type of cataract is so strong that is likely to be causal. Since inhaled corticosteroids have the potential to cause severe side effects, they should be used at the lowest doses and for the shortest possible length of time, in agreement with effective asthma management.

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