Dyspnea Doesn't Always Signify Bronchial Asthma

2 Feldman C, Kallenbach JM, Levy H, et al. Comparison of bacteraemic community-acquired pneumonia due to S pneumoniae and K pneumoniae in an intensive care unit. Respiration 1991; 58:265-70 3 Feldman C, Smith C, Levy H, et al. Klebsiella pneumoniae bacteraemis at an urban general hospital. J Infect 1990; 20:21-31 4 Hammond JMJ, Potgieter PD, Linton DM, et al. Intensive care management of community-acquired Klebsiella pneumoniae. Respir Med 1990; 84:11-6

alpha-2 interferon and viral exac.-erbations of chronic respiratory disease. Thorax 1991; 46:706-11 3 Nicholson KG, Baker DJ, Farquhar A, et al. Acute upper respiratory tract viral illness and influenza immunisation in homes for the elderly. Epidemiol Infect 1990; 105:609-18 4 Nicholson KG, Kent J, Ireland DC. Respiratory viruses and exacerbation of asthma in adults. BMJ 1993; 307:982-86

Dyspnea Doesn't Always Signify Bronchial Asthma The Contribution of Respiratory Viruses to Severe Exacerbations of Asthma in Adults To the Editor:

The question of whether respiratory viruses play a role in exacerbations of asthma is important, topical, and controversial. Identifying the cause of exacerbations will help optimize treatment and prophylaxis. Sokhandan et al (CHEST 1995; 107:1570-75) suggest that viral infection may not be as prevalent a precipitate of asthma in adults requiring emergency room treatment as is generally thought. Others may not find their data convincing. Sokhandan et al used viral culture and rapid antigen detection by fluorescent staining for all 33 patients, but serology was only undertaken for 16 of the 33. Human rhinoviruses and coronaviruses are fastidious for certain cells and growth conditions, which may explain in part their failure to identify viruses. Indeed using the same assays during the study months the Clinical Virology Laboratory at University Hospitals, Cleveland, failed to isolate any human rhinoviruses or coronaviruses, which together cause about two thirds of common colds, from other patients with respiratory symptoms. A report 1 from our unit has shown seminested reverse transcriptase polymerase chain reactions to be five times more sensitive than cell culture in detecting human rhinoviruses in samples from adults with respiratory virus infections. Other reports from our unit have also shown that enzyme linked immunosorbent assays for antibodies to human coronaviruses of groups 229E and OC43 were able to detect infection in 7 to 19% of paired serum samples from patients with upper respiratory tract infections. 1· 3 These diagnostic methods and others were subsequently applied to determine the role of respiratory viruses in exacerbation of asthma in adults. Overall44% of 61 exacerbations with a mean decrease in peak flow rate of ?50 Umin were associated with laboratory confirmed nonbacterial infections, of which the majority (78%) were caused by human rhinoviruses and coronaviruses. 4 We note with interest that 56% of the cases by Sokhandan et al had symptoms of an upper respiratory tract infection. We suspect that the use of alternative diagnostic methods would confirm that viral infections are indeed a common cause of asthma in adults requiring emergency room treatment. Ala'Eldin H. Ahmed, MD,

Karl G. Nicholson, MD, and Victoria S. Hammersley, BSc;

Department of Microbiology and Immunology, Leicester University, England REFERENCES

1 Ireland DC, KentJ, Nicholson KG. Improved detection of rhinovirus in nasal an throat swabs by semi-nested RT-PCR. J Med Virol1993; 40:96-101 2 Wiselka MJ, Nicholson KG, Kent J, et al. Prophylactic intranasal

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To the Editor:

Drs. Patel and Norman (CHEST 1995; 107:569-70) presented one case of unilateral hyperlucency with left lower lobe mass in a patient with bronchial asthma. In the abstract they wrote that the patient had a history suggestive of bronchial asthma. But we read that the patient "denied a history of fever, preceding upper respiratory tract infections, or any allergies," and also, "She gave a history of recent hospitalization for left lower lobe pneumonia a few months prior to this admission, . . ." (CHEST 1995; 107:569). Asthma has been defined by the American Thoracic Society1 as a disease characterized by hyperreactivity of the airways to various stimuli, resulting in airway obstruction that is reversible either spontaneously or as a result of treatment. From the allergist's point of view, bronchial asthma is the extreme form of bronchial allergy, 2 even if the term "asthma" is frequently applied to the dyspnea encountered in a variety of nonallergic conditions. Thus, although a precise definition of asthma has not been established, it is accepted that asthmatic patients, clinically, experience one or more of the following symptoms: cough, paroxysmal attacks of dyspnea, and wheeze or chest tightness at night, in the morning, or after exposure to a variety of environmental stimuli.3 If asthma is a syndrome, dyspnea is the main symptom. Asthma, however, is not (only) dyspnea, and not all patients reporting episodic dyspnea suffer from asthma.4 Differences between asthma and COPD are described; 5 pleural or pulmonary neoplasms are known as causes of dyspnea6 and that malignancies very rarely occur among people suffering from bronchial asthma is also known? The patient from the study by Patel and Norman never suffered from bronchial asthma (no allergens or aspecific stimuli involved; no response to 13-agonist or steroids). Simply, she had a lung cancer presenting with dyspnea. Nothing else. This presentation is common in tracheal and tracheobronchial cancer. 8 Vesicular breath sounds and crackles were clear signs of the underlying postobstructive pneumonia. As such, the case should have been reported, otherwise it is misleading the readers. Sebastiana Rizzo, MD, FCCP, Division of Pneumology, Irecs-Polielinieo S. Matteo, Pavia, Italy REFERENCES

1 Barnes PJ, Rodger IW, Thomson NC. Pathogenesis of asthma. In: Barnes PJ, Rodger IW, Thomson NC, eds. Asthma: basic mechanisms and clinical management. London, England: Academic Press, 1988; 415-44 2 Feingold BF. Introduction to clinical allergy. Springfield, Illinois: Thomas Publishers, 1973; 77 3 Scadding JG. Asthma and bronchial reactivity. BJM 1987; 294:1115-16 4 Chapman KR. Clinical aspects of asthma. In: Bone RC, ed. Current opinion in pulmonary medicine. Philadelphia: Current Science, 1995; 40-3 5 Scott JA, Mahler DA. Diagnosis of obstructive pulmonary disease Communications to the Edttor

and differentiation from asthma. In: Bone RC, ed. Current opinion in pulmonary medicine. Philadelphia: Current Science, 1995; 144-49 6 Seaton S, Seaton D, Leitch AG. Crofton and Douglas's respiratory diseases (Italian ed). Milan, Italy: McGraw-Hill, 1991; 108 7 Rizzo S. Clinical evidence that allergy protects from cancer. In: Olivieri D, Bertorellli G, DelDonno M, e t al, eds. ACCP Meeting. Bologna, Italy: Mattioli, 1992; 109-14 8 Rizzo S, Prati U, Roveda L. Epidemiology of benign and malignant tracheal tumors: a 10-year experience (1981-1990). Rass Patol Appar Respir 1993; 8:215-19

Evaluating the Bronchodilator Response in Elderly Who Have Asthma To the Editor:

We read with interest the article by Connolly and coworkers concerning the impaired bronchodilator response to albuterol in the elderly (CHEST 1995; 108:401-06). The authors demonstrated that the airway l32-adrenergic responsiveness was diminished in old age. The study is meticulously done, and the results are very impressive; however, we are not in agreement with the authors' conclusion that airway adrenoreceptor dysfunction may be implicated in late-onset asthma in the elderly. First, several investigators 1-3 have reported that there are no differences in bronchodilator responses to l32-adrenergic inhalational drugs or anticholinergic inhalational drugs between younger and older patients with asthma or obstructive lung disease. Second, the physiologic aging and pathologic aging are not the same. The current study showed the age-dependent decline in the airway l32-adrenergic responsiveness in healthy elderly persons, but not in elderly patients with asthma. Although the nonspecific airway responsiveness during aging may predispose to the development of asthma in later life, it is difficult to separate the true "age effect" from the cumulative environmental effects, including cigarette smoking. The certain relationship between age and airway hyperreactivity is also a matter of debate.4 Furthermore, inflammatory mechanisms involving the basophil are implicated in the development of increasing nonspecific airway responsiveness during aging. 5 Therefore, the results from the normal elderly subjects may not always predict the pathophysiology in elderly asthma. Third, it is suggested that long-standing asthma may lead to chronic persistent airflow obstruction in the elderly. 6 The influences of airway epithelial damage, chronic inflammation, and duration of asthma on the function of l32-adrenergic receptor should be considered for the elderly patients with asthma. A recent animal study revealed that the down-regulation and recovery of l32-adrenergic rec1,tor in heart and lung was not influenced by age in mRNA levels. Because the asthmatic patients need to use the 132-adrenergic inhalational drug over a long time, the study concerning the down-regulation of adrenoreceptor function in elderly patients with asthma may be of clinical significance. Although the data from the authors are important for the understanding of the age-related alterations in the airway adrenoreceptor function, a direct comparison between healthy elderly and asthmatic elderly regarding bronchodilator response to 132-adrenergic agonist or a longitudinal study of airway l32-adrenergic responsiveness in both asthmatic and healthy subjects may be necessary to address their hypothesis. Shinji Teranwto, MD, Yoshinosuke Fukuchi, MD, FCCP, and Yasuyoshi Ouchi, MD;

Department of Geriatrics, Faculty of Medicine, University of Tokyo, Japan Rryrint requests: Dr. Teranwto, Department of Geriatrics, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo Bunkyo-Ku, Tokyo, Japan 113 REFERENCES

1 Kradjan WA, Driesner NK, Abuan TH, e t al. Effect of age on bronchodilator response. Chest 1992; 101:154.5-51 2 Nisar M, Earis JE, Pearson MG, et al. Acute bronchodilator trials in chronic obstructive pulmonary disease. Am Rev Respir Dis 1992; 146:555-59 3 Teramoto S, Fukuchi. Improvements in exercise capacity and dyspnoea by inhaled anticholinergic drug in elderly patients with chronic obstructive pulmonary disease. Age Ageing 1995; 24:278-82 4 Davis PB, Byard PJ. Relationships among airway reactivity, pupillary a-adrenergic and cholinergic responsiveness, and age. J Appl Physiol 1988; 65:200-04 5 Sparrow D, O'Connor GT, Rosner B , et al. Predictors of longitudinal change in methacholine airway responsiveness among middle-aged and older men: the normative aging study. Am J Respir Crit Care Med 1994; 149:376-81 6 Braman SS, Kaemmerlen JT, Davis SM. Asthma in the elderly: a comparison between patients with recently acquired and longstanding disease. Am Rev Respir Dis 1991; 143:336-40 7 Raitt MH, Tamblyn C, Allen JM, et al. Beta-adrenergic receptor downregulation and recovery in heart and lung in the Fischer 344 rat: effects of aging and correlation with mRNA levels. J Gerontol 1995; 50A:B213-B217

To the Editor:

We thank Dr. Teramoto and colleagues for their comments and appreciate the opportunity to respond. Their letter makes several interesting points, and for the most part, we are in agreement. While it is true that, in the three studies quoted by Teramoto et al (CHEST 1992; 101:1545-51; Am Rev Respir Dis 1992; 146:55559; and Age Ageing 1995; 24:278-82), there were no significant differences in bronchodilator response to l32-adrenergic agonists between young and older patients with asthma, these studies involved pharmacologic doses of 13-agonist, which may have masked any subtle differences. Our study used very small doses of albuterol; and in fact, the geometric mean total doses needed to return forced expiratory flow at 50% vital capacity to its baseline value were less than 50 pg. We also agree that our current study only showed an age dependent decline in airway l32-adrenergic responses in healthy elderly people, not asthmatics. However, our previous work has suggested that the mononuclear leukocyte l32-adrenoceptor dysfunction seen in late onset asthma in the elderly is similar to that seen in normal aging. 1 Although these latter results need to be confirmed by others, they suggest that late onset asthma in part may be the end of a spectrum of age-dependent l32-adrenoceptor "decline" and that airway receptor studies in the normal elderly may be extrapolated to elderly asthmatics, albeit tentatively. With regard to downregulation or tachyphylaxis of the 132adrenoceptor system, this is clearly an important variable but probably is not the whole answer even in young patients. 2 Nevertheless, we do agree that a study to evaluate this factor in elderly asthmatics would provide important information. The symptoms of asthma are likely to be multifactorial in etiology, and a decrease in 13-agonist responsiveness may contribute to these symptoms regardless of the specific cause. Finally, we agree entirely that the relationship between age and CHEST I 109 I 2 I FEBRUARY, 1996

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