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Clinical physiologic correlates in asthma
THE JOURNAL
OF
ALLERGY CLINICAL VOLUME
IMMUNOLOGY NUMBER
77
Postgraduate
course
Clinical physiologic E. R. McFadden,
1, PART 1
correlates
Jr., M.D. Cleveland,
in asthma
Ohio
Although asthma is a disease of airways, it affects all aspects of lung function, and in acute severe episodes even cardiac performance is influenced. The typical exacerbation is characterized by symptoms of wheezing, dyspnea, and cough associated with the signs of tachycardia, tachypnea, hyperinjlation of the thorax, and stridulous breathing. Usually, the pulse rate is 100 bpm or more, and the respiratory frequence varies between 25 to 28 breaths per minute. Use of accessory muscles and pulsus paradoxicus occur in 30% to 40% of episodes. From a functional standpoint, the FEV,, peakjow, and residual volume tend to average approximately 30%, 20%, and 40% of expected values, respectively. Neither the presenting signs, symptoms, or functional abnormalities can be used to predict a relapse or the need for hospitalization because these variables do not necessarily determine the subsequent response to therapy. Furthermore, these signs and symptoms imperfectly reflect the physiologic abnormalities, and their loss can not be relied on as indicating a return to functional normalcy. (J ALLERGY CLIN IMMUNOL 77:1-j, 1986.)
The signs and symptoms of bronchial asthma are frequently dramatic and have capturedthe imagination of physicians since antiquity. For example, early in the Christian era, Aretaeus, the Cappadocianwrote: In an asthma,the cheeksare ruddy, eyesprotuberantas if from strangulation; a ralecanbe heardduringthe waking state,but the evil is muchworseduringsleep;the voice is liquid without resonance; thereis desireof muchandcold air; theyeagerlygo into the openair sinceno housesufficei for their respiration;they breathestandingasif desiringto draw in all the air they canpossiblyinhale. Whenthe From the Asthma and Allergic Disease Center and the Departments of Medicine of University Hospitals, and Case Western Reserve University School of Medicine, Cleveland, Ohio. Received for publication July 27, 1985. Accepted for publication August 7, 1985. Reprint requests: E. R. McFadden, Jr., M.D., Asthma and Allergic Disease Center, University Hospitals, 2074 Abington Rd., Cleveland, OH 44106.
Abbreviation
used
RV: Residualvolume
crisisturnsto an end, the expectorationbecomes morecopiousandricher, the urineincreases andthe voice becomes louder.’ Over the last 1600 to 1700 years, other observers have addedequally expressivedescriptions,and today the clinical featuresof asthmaare readily recognized. In spite of this long experience, however, it has only been in the previous 15 years that we have begun to understandhow the functional defects in this illness evoke their clinical manifestationsand how this information can be usedto better treat the disease.This article will review our current understandingof the clinical-physiologic correlates in asthma and their therapeutic and prognostic implications. 1
2 McFadden
DISTRIBUTION OF SIGNS AND SYMPTOMS AND FUNCTIONAL ABNORMALITIES IN ACUTELY ILL SUBJECTS WITH ASTHMA Most people with acute asthma present for therapy with a constellation of symptoms consisting of cough, dyspnea. and wheezing. Typically, these symptoms arc present simultaneously, but this need not be the case. For example, Fischl ct al.,’ in their study of 205 individuals with acute bronchial asthma, found 31 patients who were acutely ill but not short of breath. All, however. had cough and wheeze. Other variant manifestations also exist, and patients have been described with only cough or dyspnea as isolated entities.’ The physical signs associated with acute airway obstruction arc tachycardia, tachypnea. hyperinflation, wheeze. accessory muscle use, pulsus paradoxus, and diaphoresis. The last three physical signs have been reported to be associated with severe airway obstruction? hence, their presence is clinically significant and should be routinely sought. It is important to recognize, however, that the absence of a pulsus paradoxicus or accessory muscle use does not rule out the existence of major flow limitation. To be manifest. those signs require the development of large negative swings in intrathoracic pressures with respiration. Consequently, if a person is breathing rapidly and shallowly, the appropriate physiology may not be present for their expression. Because they share a common pathogenesis, pulsus paradoxicus and use of the accessory muscles of respiration tend to coexist. Since many large series concerning asthma have now been published, it is possible to determine quantitatively the types of changes in cardiopulmonary function that occur in acute asthma as well as the relative distribution of the various clinical signs associated with them. Although there is wide scatter, based on almost 600 observations in the literature, the average pulse rate in a patient requesting emergency therapy is approximately 100 bpm, and the respiratory frequency tends to vary between 2.5 to 2X breaths per minute. ‘. ’ “’ Heart rates > 120 and tachypnea with frequencies >30 are not uncommon, however, and can be found in 20% to 25% of the subjects. depending on the study.‘. ‘) “’ Use of the accessory muscles of respiration and a pulsus paradoxicus are also common and have been reported in 30% to 40% of subjects with asthma before treatment. When the latter sign is present, the fall in blood pressures with respiration is usually small, tending to average 8 to 10 mm Hg. Values > 15 mm Hg are found in <20% of patients.‘, I(‘. ” Typically, the greater the obstruction, the more abnormal each of the above clinical signs. From the standpoint of deranged function: the every day asthma attack is characterized by hyperinfation,
.I ALLERGY
::i GN. !MMUtG ,IN?IARY 19RL;
a prolonged forced expiratory time, a iow I.VC, ;II:~I marked depression of FEV and flow- r;rte :I,. *~l;j: the clinical data, there is great variabiiiry. nut the beam preserved index is the FVC followed thcrc;!!tcr b> the FEV,, maximum expiratory How rates. and rmxiitltici midexpiratory flow rates In dccreasmg order ’ 1 \i: ally, the FVC is approximately 50% of prcdictcd, tnc FEV, is approximately 30%. to 35%. and thg: how rare:, arc 20% or less. In absolute terms the FtiL / tends :I> be about i I..’ ” ” ,’ and the peak ilou about Z. ‘> 1Jsec. !. l’j During periods of acute symptoms, RV and iunctional residual capacity tend to be grossly elevated. whereas total lung capacity remains norma! or neariy so. RV tends to average 400% of predicted. wherea%, functional residual capacity- tends to bc double normal.“. ” Vital capacity and its components, inspirator? capacity and expiratory reserve volume. arc reduce%! to 50% of expected. The commonestpattern of blood gas abnormalities observed in acute asthmais a combination of hypoxemia. hypocapnia, and respiratory alkalosis.ii !’ L irtually all patientswith asthmahave hypoxemia during acute exacerbationsof their illnessand generally, the more severethe obstruction the lower the arterial oxy. gen tension. It is very unusual. however, for uncomplicated episodesof asthma to develop 0; tensions
VOLUME NUMBER
77 1, PART 1
Clinical
fore, trying to judge the extent of a given patient’s derangements in ventilatory status, on clinical grounds alone, is extremely hazardous and should not be relied on with any degree of confidence. Concurrent with the changes in pulmonary mechanics and gas exchange, individuals with acute exacerbations of asthma can also develop various electrocardiographic abnormalities.2’-23 As indicated above, most people have a sinus tachycardia. Premature ventricular contractions can be observed in a small minority of individuals, but atria1 arrhythmias are extremely rare.“. ‘3 It is of interest that as a patient’s airway obstruction is reversed, his/her tachycardia resolves despite the use of sympathomimetics. In fact, many studies have not found heart rates to rise during emergency therapy of asthma, even when nonselective B-agonists were used.7-9 Other reversible ECG abnormalities include p pulmonali, right axis deviation, right bundle branch block, clockwise rotation, and right ventricular strain patterns.21-23
CLINICAL-PHYSIOLOGIC
CORRELATES
To what extent do the signs and symptoms of asthma reflect the existing alterations in pulmonary function? Intuitively, one would anticipate a one-toone correspondence. However, this is not the case, and the available data indicate that a symptomatic and physiologic response to therapy has multiple determinants and that a complex relationship exists between the pathophysiologic and clinical features of the illness. Serial studies of the pattern of recovery demonstrate that acutely ill subjects rapidly tend to loose their complaints of breathlessness and wheezing when they are administered appropriate therapy.4 When this occurs, the use of accessory muscles and pulses paradoxicus also tend to remit rather quickly. The other objective signs of asthma such as rhonchi and wheezing take much longer to resolve and do not appear to bear a constant relationship to the patient’s symptoms. In fact, in one study when over 90% of the subjects considered themselves asymptomatic, 40% were still wheezing when they were examined.4 Analysis of pulmonary mechanical data as a function of a patient’s clinical state demonstrates that most signs and symptoms imperfectly reflect the physiologic alterations that are present4. ‘* When a patient considers his/her attack to have ended, the FEV, and RV, although they are significantly improved over pretreatment values, are still quite abnormal, averaging 50% and 200% of normal, respectively. When the signs of acute asthma have dissipated, specific conductance is approaching its normal range, but FEV,, forced expiratory flows, and RV remain grossly abnormal. The latter abnormalities frequently persist for prolonged periods, and it is not uncommon to find
physiologic
correlates
in asthma
3
flows in the midvital capacity range reduced to 50% of expected and values for RV of 150% to 200% of
normal as long as several weeks after a single exacerbation of asthma.“, 24,25 From a clinical point of view, these observations indicate that one can not rely on the loss of subjective complaints or even the sign of wheezing as indicating a return to functional normalcy and that the termination of an episode of asthma on clinical grounds in typically associated with a large reservoir of residual disease. Since this remaining obstruction limits the patients’ pulmonary reserve, it is difficult for them to readily accommodate further reductions in lung function without developing acute symptoms; hence, the presence of this obstruction may lend itself to an increase in the frequency and/or severity of subsequent episodes. Do the above observations mean that we should not listen to our patient’s perceptions of the severity of their impairments, or lack there of? Based on all considerations, the answer is no. Imperfect as the relationship between functional derangements and signs and symptoms may be, most patients are better at judging the degree of obstruction that is present than are the physicians attending them. Shim and William? asked a group of patients with asthma to estimate their peak flow rates and found that 63 were accurate to within 20% of the measured values. By contrast, only 44% of the estimates of the physicians fell within this range. It is of interest that the physicians’ inaccuracies were independent of the extent of their clinical experience. Although the observations of Shim and Williams26 are important, it should be kept in mind that some individuals are unable to sense the presence of even marked airway obstruction. Rubinfeld and Pain*’ reported a group of patients who remained asymptomatic while they were undergoing bronchoprovocation, even though their FEV, had been reduced to values ranging between 44% and 18% of normal. Fortunately, this condition is rare; however, failure to recognize that such patients exist can frequently end in tragedy. When these patients do begin to experience symptoms, their pulmonary reserve is frequently so exhausted that, unless they are properly treated, respiratory failure and death can ensue.
USE OF CLINICAL AND PHYSIOLOGIC DATA TO PREDICT THE NEED FOR HOSPITALIZATION OR THE TENDENCY TO RELAPSE There are a number of studies in the literature that have used the presenting signs, symptoms, and/or alterations in lung function in patients with asthma to attempt to predict the need for hospitalization or the tendency to relapse, but the results have been incon-
4 McFadden
elusive because of various problems in study design and/or execution.‘. ‘I. x-” In some investigations the intensity, duration, and type of therapy was not controlled, 1I. 2’).10whereas in others only a limited number of variables were examined or the prediction criteria were determined retrospectively.‘- “’ lx “’ An example of the difficulties produced by the latter approach is the investigation of Fischl et al.’ These authors developed a multifactorial prediction index based on selected clinical and physiologic variables that was reported to be 95% and 96% accurate in predicting the risk of relapse and the need for hospitalization, respectively. As indicated, the prediction index was constructed after the study was completed and after the values were chosen for use tended mainly to reflect those observed in the group of patients who were admitted or had relapses. Unfortunately, the authors did not test their index in a prospective study, and when other authors performed such tests, neither utility nor validity could be confirmed. In two studies involving more than 200 subjects, the Fischl et al. index was found to perform little better than chance alone. IfI. 31 The failure of this index is not entirely unexpected because the presenting clinical and physiologic manifestations of acute asthma do not necessarily indicate what the subsequent response to therapy will be. Patients with very similar asthma attacks can respond quite differently to the same medications depending on the cause of their obstruction.” The time course of response to therapy in asthma is biphasic with an initial fast component followed by a slow component.‘. “, “. ‘*-” The immediate phase of recovery after a bronchodilator appears to be due to the resolution of smooth muscle contraction, and patients in whom this is a major contribution to their disability respond quite nicely to minimal treatment. even if the obstruction is severe at the start.J. “ The slowly resolving stage probably represents the effects of airway inflammation with edema and impaired mucociliary transport. When this is the predominant cause of the obstruction, bronchodilators alone tend to be ineffectual, and both a longer time and more intense therapy are needed to terminate the episode and prevent relapse. Typically. such patients demonstrate an early improvement, presumably by achieving maximal or near maximal smooth muscle relaxation, but then they continue to manifest severe airway obstruction.3. ’ Such individuals can remain unresponsive to intensive bronchodilator and steroid therapy for 24 to 48 hours.” Because of the unremitting obstruction, this group accounts for most admissions to hospital,” and if they are discharged from the emer-
gency room after their early improvement. they- hail. a significant incidence of rclapsc.” ” Can such patients be detected early in their course” “’ Based on the available data the answer appears to ill* yes. The three most valuable clues for dctcction 3:~ the initial clinical findings. state of lung funcrion. 91i~l the early response to treatment. These patient\ i*nnmonly have a pulsus paradoxus and are asmg then accessory muscles of respiration. Unlike tne avrragc patient with asthma, they Jo not quickl:v lose these signs in response to aggrcsstvc therapy. In additior.. they habitually have an FEb’, of 25% ot predicted. ‘-zt less. which increases little after intenstvl: trcatmcnr, In our experience. if the FEV, does not rtse to ,,Xl’ii of normal after an hour of aggressive therapy. ilte patient will end up being admitted 45% to SE% of the time or will require prolonged stays in the mergcnc.~ room.” It is not yet known if the course of the discasc <‘an be improved in these individuals by instituting other forms of treatment as soon as they are discovered. ln most such patients glucocorticoids speed the recovery and therefore should clearly be used. ii However, since these drugs take many hours to produce their effc~!. it may be worthwhile to begin the drugs as soon as a poorly responsive patient is identified and not M’LLI! until other types of treatment have been exhausted Ultimately, appropriately controlled prospective studies will have to be carried out to evaluate the soundnc\i~ of this approach. REFERENCES I. 7.
3.
4.
5. 6. 7.
8.
9.
Adams t’: The extent works of Aretaeus the C’appadwan. London, 1856, Sydenham Society, p 3 16 Fischl MA. Pitchenik A. Gardner LB: An index predtcting relapse and need for hospitaliration in patients with acute bronchial asthma. N Engl J Med 305:783. 19X1 McFadden ER Jr: Exertional dyspnea and cough as preludes to acute attacks of bronchial asthma. N Engl J Med 292555 1975 McFadden ER Jr, Kiser R. d&root W: Acute bronchial asthma: relations between clinical and physiologic manifestations, S Engl J Med 288231, 197.1 Knowles GK, Clark TJH: Pulsus paradoxicus as a valuable sign indicating severity of asthma. Lancet 1: 1356. 197.1 Brcnner BE. Abraham E. Simon RR: Position and diaphoresri in acute asthma. Am J Med 74:1005. 1983 Rossing TH. Panta CH. Goldstein DH, Snapper JR, McFadden ER Jr: Emergency therapy of asthma: comparison of the acute effects ofparenteral and inhaled sympathomimetics and infused aminophylline. Am Rev Respir 13s 121365. !YXll Kossing TH, Fanta CH, McFadden ER Jr: A controlfcd trial of the use of single versus combined drug therapy in the treatment of acute episodes of asthma. Am Rev Respit Dis 123: 190, 19x1 Rnta CH. Rossing TH, McFadden ER Jr: Emergency room treatment of asthma. Relationships among therapeutic com-
VQLUME NUMBER
10.
11.
12.
13. 14.
15. 16. 17.
18. 19. 20.
21. 22.
77 1, PART 1
binations, severity of obstruction, and time course of response. Am 3 Med 72:416, 1982 Rose C, Murphy JG, Schwartz JS: Performance of an index predicting the response of patients with acute bronchial asthma to intensive emergency department treatment. N Engl J Med 310573, 1984 Kelsen SG, Kelsen DP, Fleegler BF, Jones RC, Rodman T: Emergency room assessment and treatment of patients with acute asthma. Am J Med 64:622, 1978 McFadden ER Jr: Asthma: airway dynamics, cardiac function, and clinical correlates. In Middleton E, Reed CE, Ellis EF, editors: Allergy principles and practice. St. Louis, 1983, The CV Mosby Co, pp 843-62 McFadden ER Jr, Lyons HA: Arterial blood gas tensions in asthma. N Engl J Med 278:1027, 1968 Rees HA, Millar JS, Donald KW: A study of the clinical course and arterial blood gas tensions of patients in status asthmaticus. Q J Med 37:541, 1968 Miyamoto T, Mizuno K, Furuya K: Arterial blood gases in bronchial asthma. J ALLERGY CLIN IMMUNOL 45:248, 1970 Tai E, Read J: Blood gas tension in bronchial asthma. Lancet 1:644, 1967 Weng TR, Langer HM, Featherby EA, Levison H: Arterial blood gas tensions and acid-base balance in symptomatic and asymptomatic asthma in childhood. Am Rev Respir Dis 101:274, 1970 Bond E, Williams MH Jr: Severe asthma. NY State J Med 77:350, 1977 Appel D, Rubenstein R, Schrager K, Williams MH Jr: Lactic acidosis in severe asthma. Am J Med 75580, 1983 Nogrady SG, Hartley JPR, Seaton A: Metabolic effects of intravenous salbutamol in the course of acute severe asthma. Thorax 32:559, 1977 Rebuck AS, Read J: Assessment and management of severe asthma. Am J Med 51:788, 1971 Gelb AF, Lyons HA, Fairshter RD, Glauser FL, Morrissey R, Chetty K, Shiffman P: P Pulmonale in status asthmaticus. J ALLERGY CLIN IMMUNOL 64: 18, 1979
Clinical
physiologic
correlates
in asthma
5
23. Grossman J: The occurrence of arrhythmias in hospitalized asthmatic patients. J ALLERGY CLIN IMMUNOL 57:310, 1976 24. McFadden ER Jr: The chronicity of acute attacks of asthma: mechanical and therapeutic implications. J ALLERGY CLIN IMMUNOL 56:18, 1975 25. Weng TR, Levinson H: Pulmonary function in children with asthma at acute attack and symptom-free status. Am Rev Respir Dis 99:719, 1969 26. Shim CS, Williams MH Jr: Evaluation of the severity of asthma: patients vs. physician. Am J Med 68: 11, 1980 27. Rubinfeld AR, Pain CF: Perception of asthma. Lancet 1:882, 1976 28. Banner AS, Shah RS, Addington WW: Rapid prediction of need for hospitalization in acute asthma. JAMA 235:1337, 1976 29. Nowak RM, Pensler MI, Sarkar D, Anderson JA, Kvale PA, Ortiz AE, Tomlanovich MC: Comparison of peak expiratory flow and FEV, admission criteria for acute bronchial asthma. Ann Emerg Med 1164, 1982 30. Martin TG, Elenbaas RM, Pingleton SH: Failure of peak expiratory flow rate to predict hospital admission in acute asthma. Ann Emerg Med 11:466, 1982 31. Centor RM, Yarbrough B, Wood JP: Inability to predict relapse in acute asthma. N Engl J Med 310:577, 1984 32. McFadden ER Jr, Lyons HA: Serial studies of factors influencing airway dynamics during recovery from acute asthma attacks. J Appl Physiol 27:452, 1969 33. Cade JF, Woolcock AF, Rebuck AS, Pain MC: Lung mechanics during provocation of asthma. Clin Sci 40:381, 1971 34. Nowak RM, Gordon KR, Wroblewski DA, Tomlanovich MC, Kvale PA: Spirometric evaluation of acute bronchial asthma. JACEP 8:9, 1979 35. Fanta CH, Rossing TH, McFadden ER Jr: Glucocorticoids in acute asthma. A critical controlled trial. Am J Med 74:845, 1983
OF
ALLERGY CLINICAL VOLUME
IMMUNOLOGY NUMBER
77
Postgraduate
course
Clinical physiologic E. R. McFadden,
1, PART 1
correlates
Jr., M.D. Cleveland,
in asthma
Ohio
Although asthma is a disease of airways, it affects all aspects of lung function, and in acute severe episodes even cardiac performance is influenced. The typical exacerbation is characterized by symptoms of wheezing, dyspnea, and cough associated with the signs of tachycardia, tachypnea, hyperinjlation of the thorax, and stridulous breathing. Usually, the pulse rate is 100 bpm or more, and the respiratory frequence varies between 25 to 28 breaths per minute. Use of accessory muscles and pulsus paradoxicus occur in 30% to 40% of episodes. From a functional standpoint, the FEV,, peakjow, and residual volume tend to average approximately 30%, 20%, and 40% of expected values, respectively. Neither the presenting signs, symptoms, or functional abnormalities can be used to predict a relapse or the need for hospitalization because these variables do not necessarily determine the subsequent response to therapy. Furthermore, these signs and symptoms imperfectly reflect the physiologic abnormalities, and their loss can not be relied on as indicating a return to functional normalcy. (J ALLERGY CLIN IMMUNOL 77:1-j, 1986.)
The signs and symptoms of bronchial asthma are frequently dramatic and have capturedthe imagination of physicians since antiquity. For example, early in the Christian era, Aretaeus, the Cappadocianwrote: In an asthma,the cheeksare ruddy, eyesprotuberantas if from strangulation; a ralecanbe heardduringthe waking state,but the evil is muchworseduringsleep;the voice is liquid without resonance; thereis desireof muchandcold air; theyeagerlygo into the openair sinceno housesufficei for their respiration;they breathestandingasif desiringto draw in all the air they canpossiblyinhale. Whenthe From the Asthma and Allergic Disease Center and the Departments of Medicine of University Hospitals, and Case Western Reserve University School of Medicine, Cleveland, Ohio. Received for publication July 27, 1985. Accepted for publication August 7, 1985. Reprint requests: E. R. McFadden, Jr., M.D., Asthma and Allergic Disease Center, University Hospitals, 2074 Abington Rd., Cleveland, OH 44106.
Abbreviation
used
RV: Residualvolume
crisisturnsto an end, the expectorationbecomes morecopiousandricher, the urineincreases andthe voice becomes louder.’ Over the last 1600 to 1700 years, other observers have addedequally expressivedescriptions,and today the clinical featuresof asthmaare readily recognized. In spite of this long experience, however, it has only been in the previous 15 years that we have begun to understandhow the functional defects in this illness evoke their clinical manifestationsand how this information can be usedto better treat the disease.This article will review our current understandingof the clinical-physiologic correlates in asthma and their therapeutic and prognostic implications. 1
2 McFadden
DISTRIBUTION OF SIGNS AND SYMPTOMS AND FUNCTIONAL ABNORMALITIES IN ACUTELY ILL SUBJECTS WITH ASTHMA Most people with acute asthma present for therapy with a constellation of symptoms consisting of cough, dyspnea. and wheezing. Typically, these symptoms arc present simultaneously, but this need not be the case. For example, Fischl ct al.,’ in their study of 205 individuals with acute bronchial asthma, found 31 patients who were acutely ill but not short of breath. All, however. had cough and wheeze. Other variant manifestations also exist, and patients have been described with only cough or dyspnea as isolated entities.’ The physical signs associated with acute airway obstruction arc tachycardia, tachypnea. hyperinflation, wheeze. accessory muscle use, pulsus paradoxus, and diaphoresis. The last three physical signs have been reported to be associated with severe airway obstruction? hence, their presence is clinically significant and should be routinely sought. It is important to recognize, however, that the absence of a pulsus paradoxicus or accessory muscle use does not rule out the existence of major flow limitation. To be manifest. those signs require the development of large negative swings in intrathoracic pressures with respiration. Consequently, if a person is breathing rapidly and shallowly, the appropriate physiology may not be present for their expression. Because they share a common pathogenesis, pulsus paradoxicus and use of the accessory muscles of respiration tend to coexist. Since many large series concerning asthma have now been published, it is possible to determine quantitatively the types of changes in cardiopulmonary function that occur in acute asthma as well as the relative distribution of the various clinical signs associated with them. Although there is wide scatter, based on almost 600 observations in the literature, the average pulse rate in a patient requesting emergency therapy is approximately 100 bpm, and the respiratory frequency tends to vary between 2.5 to 2X breaths per minute. ‘. ’ “’ Heart rates > 120 and tachypnea with frequencies >30 are not uncommon, however, and can be found in 20% to 25% of the subjects. depending on the study.‘. ‘) “’ Use of the accessory muscles of respiration and a pulsus paradoxicus are also common and have been reported in 30% to 40% of subjects with asthma before treatment. When the latter sign is present, the fall in blood pressures with respiration is usually small, tending to average 8 to 10 mm Hg. Values > 15 mm Hg are found in <20% of patients.‘, I(‘. ” Typically, the greater the obstruction, the more abnormal each of the above clinical signs. From the standpoint of deranged function: the every day asthma attack is characterized by hyperinfation,
.I ALLERGY
::i GN. !MMUtG ,IN?IARY 19RL;
a prolonged forced expiratory time, a iow I.VC, ;II:~I marked depression of FEV and flow- r;rte :I,. *~l;j: the clinical data, there is great variabiiiry. nut the beam preserved index is the FVC followed thcrc;!!tcr b> the FEV,, maximum expiratory How rates. and rmxiitltici midexpiratory flow rates In dccreasmg order ’ 1 \i: ally, the FVC is approximately 50% of prcdictcd, tnc FEV, is approximately 30%. to 35%. and thg: how rare:, arc 20% or less. In absolute terms the FtiL / tends :I> be about i I..’ ” ” ,’ and the peak ilou about Z. ‘> 1Jsec. !. l’j During periods of acute symptoms, RV and iunctional residual capacity tend to be grossly elevated. whereas total lung capacity remains norma! or neariy so. RV tends to average 400% of predicted. wherea%, functional residual capacity- tends to bc double normal.“. ” Vital capacity and its components, inspirator? capacity and expiratory reserve volume. arc reduce%! to 50% of expected. The commonestpattern of blood gas abnormalities observed in acute asthmais a combination of hypoxemia. hypocapnia, and respiratory alkalosis.ii !’ L irtually all patientswith asthmahave hypoxemia during acute exacerbationsof their illnessand generally, the more severethe obstruction the lower the arterial oxy. gen tension. It is very unusual. however, for uncomplicated episodesof asthma to develop 0; tensions
VOLUME NUMBER
77 1, PART 1
Clinical
fore, trying to judge the extent of a given patient’s derangements in ventilatory status, on clinical grounds alone, is extremely hazardous and should not be relied on with any degree of confidence. Concurrent with the changes in pulmonary mechanics and gas exchange, individuals with acute exacerbations of asthma can also develop various electrocardiographic abnormalities.2’-23 As indicated above, most people have a sinus tachycardia. Premature ventricular contractions can be observed in a small minority of individuals, but atria1 arrhythmias are extremely rare.“. ‘3 It is of interest that as a patient’s airway obstruction is reversed, his/her tachycardia resolves despite the use of sympathomimetics. In fact, many studies have not found heart rates to rise during emergency therapy of asthma, even when nonselective B-agonists were used.7-9 Other reversible ECG abnormalities include p pulmonali, right axis deviation, right bundle branch block, clockwise rotation, and right ventricular strain patterns.21-23
CLINICAL-PHYSIOLOGIC
CORRELATES
To what extent do the signs and symptoms of asthma reflect the existing alterations in pulmonary function? Intuitively, one would anticipate a one-toone correspondence. However, this is not the case, and the available data indicate that a symptomatic and physiologic response to therapy has multiple determinants and that a complex relationship exists between the pathophysiologic and clinical features of the illness. Serial studies of the pattern of recovery demonstrate that acutely ill subjects rapidly tend to loose their complaints of breathlessness and wheezing when they are administered appropriate therapy.4 When this occurs, the use of accessory muscles and pulses paradoxicus also tend to remit rather quickly. The other objective signs of asthma such as rhonchi and wheezing take much longer to resolve and do not appear to bear a constant relationship to the patient’s symptoms. In fact, in one study when over 90% of the subjects considered themselves asymptomatic, 40% were still wheezing when they were examined.4 Analysis of pulmonary mechanical data as a function of a patient’s clinical state demonstrates that most signs and symptoms imperfectly reflect the physiologic alterations that are present4. ‘* When a patient considers his/her attack to have ended, the FEV, and RV, although they are significantly improved over pretreatment values, are still quite abnormal, averaging 50% and 200% of normal, respectively. When the signs of acute asthma have dissipated, specific conductance is approaching its normal range, but FEV,, forced expiratory flows, and RV remain grossly abnormal. The latter abnormalities frequently persist for prolonged periods, and it is not uncommon to find
physiologic
correlates
in asthma
3
flows in the midvital capacity range reduced to 50% of expected and values for RV of 150% to 200% of
normal as long as several weeks after a single exacerbation of asthma.“, 24,25 From a clinical point of view, these observations indicate that one can not rely on the loss of subjective complaints or even the sign of wheezing as indicating a return to functional normalcy and that the termination of an episode of asthma on clinical grounds in typically associated with a large reservoir of residual disease. Since this remaining obstruction limits the patients’ pulmonary reserve, it is difficult for them to readily accommodate further reductions in lung function without developing acute symptoms; hence, the presence of this obstruction may lend itself to an increase in the frequency and/or severity of subsequent episodes. Do the above observations mean that we should not listen to our patient’s perceptions of the severity of their impairments, or lack there of? Based on all considerations, the answer is no. Imperfect as the relationship between functional derangements and signs and symptoms may be, most patients are better at judging the degree of obstruction that is present than are the physicians attending them. Shim and William? asked a group of patients with asthma to estimate their peak flow rates and found that 63 were accurate to within 20% of the measured values. By contrast, only 44% of the estimates of the physicians fell within this range. It is of interest that the physicians’ inaccuracies were independent of the extent of their clinical experience. Although the observations of Shim and Williams26 are important, it should be kept in mind that some individuals are unable to sense the presence of even marked airway obstruction. Rubinfeld and Pain*’ reported a group of patients who remained asymptomatic while they were undergoing bronchoprovocation, even though their FEV, had been reduced to values ranging between 44% and 18% of normal. Fortunately, this condition is rare; however, failure to recognize that such patients exist can frequently end in tragedy. When these patients do begin to experience symptoms, their pulmonary reserve is frequently so exhausted that, unless they are properly treated, respiratory failure and death can ensue.
USE OF CLINICAL AND PHYSIOLOGIC DATA TO PREDICT THE NEED FOR HOSPITALIZATION OR THE TENDENCY TO RELAPSE There are a number of studies in the literature that have used the presenting signs, symptoms, and/or alterations in lung function in patients with asthma to attempt to predict the need for hospitalization or the tendency to relapse, but the results have been incon-
4 McFadden
elusive because of various problems in study design and/or execution.‘. ‘I. x-” In some investigations the intensity, duration, and type of therapy was not controlled, 1I. 2’).10whereas in others only a limited number of variables were examined or the prediction criteria were determined retrospectively.‘- “’ lx “’ An example of the difficulties produced by the latter approach is the investigation of Fischl et al.’ These authors developed a multifactorial prediction index based on selected clinical and physiologic variables that was reported to be 95% and 96% accurate in predicting the risk of relapse and the need for hospitalization, respectively. As indicated, the prediction index was constructed after the study was completed and after the values were chosen for use tended mainly to reflect those observed in the group of patients who were admitted or had relapses. Unfortunately, the authors did not test their index in a prospective study, and when other authors performed such tests, neither utility nor validity could be confirmed. In two studies involving more than 200 subjects, the Fischl et al. index was found to perform little better than chance alone. IfI. 31 The failure of this index is not entirely unexpected because the presenting clinical and physiologic manifestations of acute asthma do not necessarily indicate what the subsequent response to therapy will be. Patients with very similar asthma attacks can respond quite differently to the same medications depending on the cause of their obstruction.” The time course of response to therapy in asthma is biphasic with an initial fast component followed by a slow component.‘. “, “. ‘*-” The immediate phase of recovery after a bronchodilator appears to be due to the resolution of smooth muscle contraction, and patients in whom this is a major contribution to their disability respond quite nicely to minimal treatment. even if the obstruction is severe at the start.J. “ The slowly resolving stage probably represents the effects of airway inflammation with edema and impaired mucociliary transport. When this is the predominant cause of the obstruction, bronchodilators alone tend to be ineffectual, and both a longer time and more intense therapy are needed to terminate the episode and prevent relapse. Typically. such patients demonstrate an early improvement, presumably by achieving maximal or near maximal smooth muscle relaxation, but then they continue to manifest severe airway obstruction.3. ’ Such individuals can remain unresponsive to intensive bronchodilator and steroid therapy for 24 to 48 hours.” Because of the unremitting obstruction, this group accounts for most admissions to hospital,” and if they are discharged from the emer-
gency room after their early improvement. they- hail. a significant incidence of rclapsc.” ” Can such patients be detected early in their course” “’ Based on the available data the answer appears to ill* yes. The three most valuable clues for dctcction 3:~ the initial clinical findings. state of lung funcrion. 91i~l the early response to treatment. These patient\ i*nnmonly have a pulsus paradoxus and are asmg then accessory muscles of respiration. Unlike tne avrragc patient with asthma, they Jo not quickl:v lose these signs in response to aggrcsstvc therapy. In additior.. they habitually have an FEb’, of 25% ot predicted. ‘-zt less. which increases little after intenstvl: trcatmcnr, In our experience. if the FEV, does not rtse to ,,Xl’ii of normal after an hour of aggressive therapy. ilte patient will end up being admitted 45% to SE% of the time or will require prolonged stays in the mergcnc.~ room.” It is not yet known if the course of the discasc <‘an be improved in these individuals by instituting other forms of treatment as soon as they are discovered. ln most such patients glucocorticoids speed the recovery and therefore should clearly be used. ii However, since these drugs take many hours to produce their effc~!. it may be worthwhile to begin the drugs as soon as a poorly responsive patient is identified and not M’LLI! until other types of treatment have been exhausted Ultimately, appropriately controlled prospective studies will have to be carried out to evaluate the soundnc\i~ of this approach. REFERENCES I. 7.
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23. Grossman J: The occurrence of arrhythmias in hospitalized asthmatic patients. J ALLERGY CLIN IMMUNOL 57:310, 1976 24. McFadden ER Jr: The chronicity of acute attacks of asthma: mechanical and therapeutic implications. J ALLERGY CLIN IMMUNOL 56:18, 1975 25. Weng TR, Levinson H: Pulmonary function in children with asthma at acute attack and symptom-free status. Am Rev Respir Dis 99:719, 1969 26. Shim CS, Williams MH Jr: Evaluation of the severity of asthma: patients vs. physician. Am J Med 68: 11, 1980 27. Rubinfeld AR, Pain CF: Perception of asthma. Lancet 1:882, 1976 28. Banner AS, Shah RS, Addington WW: Rapid prediction of need for hospitalization in acute asthma. JAMA 235:1337, 1976 29. Nowak RM, Pensler MI, Sarkar D, Anderson JA, Kvale PA, Ortiz AE, Tomlanovich MC: Comparison of peak expiratory flow and FEV, admission criteria for acute bronchial asthma. Ann Emerg Med 1164, 1982 30. Martin TG, Elenbaas RM, Pingleton SH: Failure of peak expiratory flow rate to predict hospital admission in acute asthma. Ann Emerg Med 11:466, 1982 31. Centor RM, Yarbrough B, Wood JP: Inability to predict relapse in acute asthma. N Engl J Med 310:577, 1984 32. McFadden ER Jr, Lyons HA: Serial studies of factors influencing airway dynamics during recovery from acute asthma attacks. J Appl Physiol 27:452, 1969 33. Cade JF, Woolcock AF, Rebuck AS, Pain MC: Lung mechanics during provocation of asthma. Clin Sci 40:381, 1971 34. Nowak RM, Gordon KR, Wroblewski DA, Tomlanovich MC, Kvale PA: Spirometric evaluation of acute bronchial asthma. JACEP 8:9, 1979 35. Fanta CH, Rossing TH, McFadden ER Jr: Glucocorticoids in acute asthma. A critical controlled trial. Am J Med 74:845, 1983