The use of bronchoprovocation in the diagnosis of hypersensitivity pneumonitis Jordan
N. Fink, M.D. Milwaukee, Wis.
Bronchoprovocation is useful as a diagnostic tool in the group of diseases known as “hypersensitivity pneumonitis” which are due to the inhalation of any of a wide variety of organic dusts found in the environment. The variety of dust antigens is continually expanding to include bacterial, fungal, protein, and even chemical antigens. The inhalation of these antigens may cause such diseases as farmer’s lung (thermophilic actinomyces), cheese-washer’s lung (Penicilliurn mseii), air-conditioner or humidifier lung (ameba, thermophilic actinomyces), bathtub-refinisher’s lung (toluene diisocyanate), or pigeon-breed-
er’s lung (avian proteins).’ Hypersensitivity pneumonitis temic as well as respiratory
oc-
ities.” While the disease usually presents as recurrent
flu-like episodes, a few individuals may develop progressive pulmonary impairment leading to irreversible pulmonary damage. It is this latter course of hypersensitivity pneumonitis that makes the diagnosis so important. Further, since avoidance of the offend-
ing antigen may be all the therapy necessary to effect a complete cure, all diagnostic measures should be utilized in uncovering the cause of the patient’s illness.
Hypersensitivity
pneumonitis should be suspected respiratory
and systemic
symptoms or in individuals with chronic respiratory symptoms and progressive pulmonary disability. The physical
examination
bodies to a suspected antigen; however,
since up to
50% of exposed but well individuals may have similar precipitins, that finding must be carefully correlated clinically. Therefore, historical data are most important in providing the clue as to a possible cause for the hypersensitivity pneumonitis.’ Bronchoprovocation may then be used as an adjunct, but with caution because of the potential severe acute episode it may induce.
presents with sys-
signs and symptoms
curring 4 to 6 hr after exposure to the sensitizing agent. The disorder is associated with multiple pulmonary function, x-ray, and immunologic abnormal-
in patients with intermittent
tosis in the acute phase, and the x-ray may show variable nodular infiltrates depending on the chronicity of the disease and frequency of episodes. Serologic evaluation may demonstrate precipitating anti-
may not be of much help, ex-
cept in the acute phase when bibasilar rales are heard; the laboratory examination may demonstrate leukocy-
TECHNIQUE Challenge can be carried out by using the patient’s own environment (pigeon coop) or by bringing the patient’s environment to the laboratory (humidifier water in DeVilbiss nebulizer). It is important to remember that if an induced acute episode is severe. corticosteroid therapy may be the only means of aborting the attack. Antihistamines and bronchodilators are of no value. Patients are studied initially before challenge with complete baseline pulmonary function tests including spirometry, lung volumes, diffusion capacity, and exercise studies. A methacholine challenge utilizing graded doses of the drug is also carried out to determine if the patient may have an irritable airway. Other baseline studies include temperature, white blood cell count, and chest x-ray. Challenge with the suspect material is then carried out over a 1%min period using methods or means that most clearly simulate natural exposure. Serial pulmonary functions, white cell counts, temperature. and chest examinations are done for a minimum of 12 hr. A significant change in pulmonary function parameters. elevation in white blood cell count, and reproduction of the patient’s symptoms indicate a positive challenge and should confirm the diagnosis of hypersensitivity
pneumonitis.
TYPES OF RESPONSES From the Allergy Section, Department of Medicine, The Medical College of Wisconsin, and the Research Service, Wood VA Center. Supported by SCOR Grant HL 15389 from the National Heart, Lung and Blood Institute; Clinical Research Center Grant RR88 at Milwaukee County Medical Complex; and the Veterans Administration. Reprint requests to: Jordan N. Fink. M.D.. Research Service, Wood VA Center. Wood, WI 53 193. Vol.
64, No. 6, Part
2, pp. 590-591
Several different types of responses to bronchial challenge may be seen in patients with hypersensitivity pneumonitis. The immediate obstructive airway response is characteristic of asthma and it alone is not observed in patients with hypersensitivity pneumonitis. The late response (Fig. I) is the common response
VOLUME NUMBER
64 6 PART 2
Diagnosis
of hypersensitivity
pneumonitis
591
FVC =jJ
tt /I12
’
,C”AllENGE CONTlOL 0,CO 35 WBC 4200 TEMP F 98b
’
’ 3
’ 4
’
‘0200 100
’
’
’
I”
0
9
20 18750 1034
f 24
9000 986
FIG. 1. Late-onset response in patient with hypersensitivity pneumonitis following challenge. Note elevation of white blood cell count (WBC) and temperature, and reduction in FVC (forced vital capacity), FEV,., (forced expiratory volume in 1 set), and DLCO (gas transfer factor).
associated with reproduction of symptoms of the acute episode of hypersensitivity pneumonitis. Four to six hours after challenge there is a reduction in forced vital capacity with a proportional reduction in forced expiratory volume in 1 set, suggestive of a restrictive defect. With severe reactions, the diffusing capacity may also be reduced and the PaOz may fall. This late reaction responds poorly to bronchodilators but can be aborted with corticosteroids. The dual response (Fig. 2) is a combination of an immediate obstructive phase, which is responsive to bronchodilators and which usually lasts less than 1 hr, followed in 4 to 6 hr by the late response and acute symptoms as described previously. Such patients do not complain of immediate symptoms and the significance of the immediate pulmonary function changes is not yet known, though they may indicate a triggering mechanism. Once the bronchoprovocation test is positive, the diagnosis should be confirmed by avoidance of exposure to the offending dust and careful clinical and physiologic reevaluation at intervals over the next several months. If the bronchoprovocation does not reproduce the entire clinical attack, then avoidance should be tried and follow-up studies carried out. It is difficuIt to purposefully challenge patients with
:H*LLINGB ‘NTWIL OLCO 37 wac 5500 TEMP F 980
7
9000
100’
0
9
22 12500
103’
FIG. 2. Dual response (immediate and late) after lenge. (Abbreviations as in Fig. 1.)
6250 980
chal-
possible hypersensitivity pneumonitis with control antigens (antigens to which they are not ordinarily exposed) because of potential sensitization to these antigens; thus control challenges are not done in these patients and the clinical changes brought about by avoidance are relied upon to confirm the diagnosis. However, the specificity of the bronchoprovocation test has been demonstrated by others,:’ and in individuals who are naturally exposed to the antigen but who are clinically well, purposeful challenge leads to no detectable changes other than an occasional elevation in white blood cell c0unt.l Thus, bronchoprovocation may be a useful adjunct in the diagnosis of hypersensitivity pneumonitis, but must be used with caution and interpreted with care. The author thanks Barbara Miller for her technical assistance and Mavis Baurle for her editorial efforts. REFERENCES I. Schatz M, Patterson R. Fink JN: Immunologic lung disease. N Engl J Med 300:1310, 1979. 2. Fink JN: Hypersensitivity pneumonitis. J AILERG\ CLIN Iw ML’NOI. 52:309. 1973. 3. Pepys .I: Hypersensitivity diseases of the lungs due to fungi and other organic dusts. Basel, 1969. S. Kargen AG, pp. 69-137. 4. Rodey GE. Fink J, Koethe S, Schlueter D, Witkowski J, Beltonville P, Rimm A. Moore V: A Study of HLA-A, B, C and DR specificities in pigeon breeder’s disease. Am Rev Respir Dis 119:755, 1979.
N. Fink, M.D. Milwaukee, Wis.
Bronchoprovocation is useful as a diagnostic tool in the group of diseases known as “hypersensitivity pneumonitis” which are due to the inhalation of any of a wide variety of organic dusts found in the environment. The variety of dust antigens is continually expanding to include bacterial, fungal, protein, and even chemical antigens. The inhalation of these antigens may cause such diseases as farmer’s lung (thermophilic actinomyces), cheese-washer’s lung (Penicilliurn mseii), air-conditioner or humidifier lung (ameba, thermophilic actinomyces), bathtub-refinisher’s lung (toluene diisocyanate), or pigeon-breed-
er’s lung (avian proteins).’ Hypersensitivity pneumonitis temic as well as respiratory
oc-
ities.” While the disease usually presents as recurrent
flu-like episodes, a few individuals may develop progressive pulmonary impairment leading to irreversible pulmonary damage. It is this latter course of hypersensitivity pneumonitis that makes the diagnosis so important. Further, since avoidance of the offend-
ing antigen may be all the therapy necessary to effect a complete cure, all diagnostic measures should be utilized in uncovering the cause of the patient’s illness.
Hypersensitivity
pneumonitis should be suspected respiratory
and systemic
symptoms or in individuals with chronic respiratory symptoms and progressive pulmonary disability. The physical
examination
bodies to a suspected antigen; however,
since up to
50% of exposed but well individuals may have similar precipitins, that finding must be carefully correlated clinically. Therefore, historical data are most important in providing the clue as to a possible cause for the hypersensitivity pneumonitis.’ Bronchoprovocation may then be used as an adjunct, but with caution because of the potential severe acute episode it may induce.
presents with sys-
signs and symptoms
curring 4 to 6 hr after exposure to the sensitizing agent. The disorder is associated with multiple pulmonary function, x-ray, and immunologic abnormal-
in patients with intermittent
tosis in the acute phase, and the x-ray may show variable nodular infiltrates depending on the chronicity of the disease and frequency of episodes. Serologic evaluation may demonstrate precipitating anti-
may not be of much help, ex-
cept in the acute phase when bibasilar rales are heard; the laboratory examination may demonstrate leukocy-
TECHNIQUE Challenge can be carried out by using the patient’s own environment (pigeon coop) or by bringing the patient’s environment to the laboratory (humidifier water in DeVilbiss nebulizer). It is important to remember that if an induced acute episode is severe. corticosteroid therapy may be the only means of aborting the attack. Antihistamines and bronchodilators are of no value. Patients are studied initially before challenge with complete baseline pulmonary function tests including spirometry, lung volumes, diffusion capacity, and exercise studies. A methacholine challenge utilizing graded doses of the drug is also carried out to determine if the patient may have an irritable airway. Other baseline studies include temperature, white blood cell count, and chest x-ray. Challenge with the suspect material is then carried out over a 1%min period using methods or means that most clearly simulate natural exposure. Serial pulmonary functions, white cell counts, temperature. and chest examinations are done for a minimum of 12 hr. A significant change in pulmonary function parameters. elevation in white blood cell count, and reproduction of the patient’s symptoms indicate a positive challenge and should confirm the diagnosis of hypersensitivity
pneumonitis.
TYPES OF RESPONSES From the Allergy Section, Department of Medicine, The Medical College of Wisconsin, and the Research Service, Wood VA Center. Supported by SCOR Grant HL 15389 from the National Heart, Lung and Blood Institute; Clinical Research Center Grant RR88 at Milwaukee County Medical Complex; and the Veterans Administration. Reprint requests to: Jordan N. Fink. M.D.. Research Service, Wood VA Center. Wood, WI 53 193. Vol.
64, No. 6, Part
2, pp. 590-591
Several different types of responses to bronchial challenge may be seen in patients with hypersensitivity pneumonitis. The immediate obstructive airway response is characteristic of asthma and it alone is not observed in patients with hypersensitivity pneumonitis. The late response (Fig. I) is the common response
VOLUME NUMBER
64 6 PART 2
Diagnosis
of hypersensitivity
pneumonitis
591
FVC =jJ
tt /I12
’
,C”AllENGE CONTlOL 0,CO 35 WBC 4200 TEMP F 98b
’
’ 3
’ 4
’
‘0200 100
’
’
’
I”
0
9
20 18750 1034
f 24
9000 986
FIG. 1. Late-onset response in patient with hypersensitivity pneumonitis following challenge. Note elevation of white blood cell count (WBC) and temperature, and reduction in FVC (forced vital capacity), FEV,., (forced expiratory volume in 1 set), and DLCO (gas transfer factor).
associated with reproduction of symptoms of the acute episode of hypersensitivity pneumonitis. Four to six hours after challenge there is a reduction in forced vital capacity with a proportional reduction in forced expiratory volume in 1 set, suggestive of a restrictive defect. With severe reactions, the diffusing capacity may also be reduced and the PaOz may fall. This late reaction responds poorly to bronchodilators but can be aborted with corticosteroids. The dual response (Fig. 2) is a combination of an immediate obstructive phase, which is responsive to bronchodilators and which usually lasts less than 1 hr, followed in 4 to 6 hr by the late response and acute symptoms as described previously. Such patients do not complain of immediate symptoms and the significance of the immediate pulmonary function changes is not yet known, though they may indicate a triggering mechanism. Once the bronchoprovocation test is positive, the diagnosis should be confirmed by avoidance of exposure to the offending dust and careful clinical and physiologic reevaluation at intervals over the next several months. If the bronchoprovocation does not reproduce the entire clinical attack, then avoidance should be tried and follow-up studies carried out. It is difficuIt to purposefully challenge patients with
:H*LLINGB ‘NTWIL OLCO 37 wac 5500 TEMP F 980
7
9000
100’
0
9
22 12500
103’
FIG. 2. Dual response (immediate and late) after lenge. (Abbreviations as in Fig. 1.)
6250 980
chal-
possible hypersensitivity pneumonitis with control antigens (antigens to which they are not ordinarily exposed) because of potential sensitization to these antigens; thus control challenges are not done in these patients and the clinical changes brought about by avoidance are relied upon to confirm the diagnosis. However, the specificity of the bronchoprovocation test has been demonstrated by others,:’ and in individuals who are naturally exposed to the antigen but who are clinically well, purposeful challenge leads to no detectable changes other than an occasional elevation in white blood cell c0unt.l Thus, bronchoprovocation may be a useful adjunct in the diagnosis of hypersensitivity pneumonitis, but must be used with caution and interpreted with care. The author thanks Barbara Miller for her technical assistance and Mavis Baurle for her editorial efforts. REFERENCES I. Schatz M, Patterson R. Fink JN: Immunologic lung disease. N Engl J Med 300:1310, 1979. 2. Fink JN: Hypersensitivity pneumonitis. J AILERG\ CLIN Iw ML’NOI. 52:309. 1973. 3. Pepys .I: Hypersensitivity diseases of the lungs due to fungi and other organic dusts. Basel, 1969. S. Kargen AG, pp. 69-137. 4. Rodey GE. Fink J, Koethe S, Schlueter D, Witkowski J, Beltonville P, Rimm A. Moore V: A Study of HLA-A, B, C and DR specificities in pigeon breeder’s disease. Am Rev Respir Dis 119:755, 1979.
