But could such a less selective group, more compa­rable to a practical clinical setting, be used to establish sensitivity and specificity for challenge testing? Un­fortunately, there is no gold standard for the diagnosis of bronchial asthma, as there is for coronary artery disease or pulmonary embolism, where coronary and pulmonary angiography are considered diagnostic. If a heterogeneous, overlapping population base were used to establish sensitivities and specificities for challenge testing, there would be doubt as to the diagnosis in many cases, and the values of these parameters would therefore be suspect.

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Since provocation testing usually continues until a positive test occurs or until approximately 200 CBU have been administered, we have presented only a single, 224 CBU curve for a negative test. The asthmatic patients of Casale et al were selected so that all had a positive test at this level or below. Studies on unselected adult asthmatic patients suggest that 100 percent sensitivity at this level is a reasonable expectation. Cockroft et al have shown similar results for histamine challenge. However, 100 percent sensitivity at this level has not been a universal finding, and we have chosen to use a sensitivity of 90 percent for the 224 CBU negative test, a more conservative approach.

These curves show 100 percent post-test probability of asthma for positive tests at low CBU, especially for the nonsmokers. This reflects the highly selective nature of the data base, with no false positives (100 percent specificity), a highly unlikely situation in a true clinical setting.

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The resulting curves are shown in Figure 1. The pretest probability is shown on the abscissa, the post- test probability on the ordinate. As an example, suppose a physician estimated that a nonsmoker had a 50 percent likelihood of asthma on the basis of history, physical examination, and laboratory infor­mation. If a methacholine challenge test showed a PD20 of 49.5 CBU, the curve for nonsmokers at a pretest probability of 0.5 shows that the post-test likelihood of asthma is approximately 90 percent.

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The data of Casale and associates for nonatopic asymptomatic cigarette smokers and nonsmokers with and without asthma were used for the analysis. The nonsmoking nonasthmatic group excluded patients with an atopic or allergic background or with positive skin tests.

Sensitivity (SE) is defined as the fraction of patients with the disease who have a positive test. Specificity (SP) is defined as the fraction of patients without the disease who have a negative test. The pretest probability (P) is the physicians estimate (in fractional terms) of the likelihood that the patient has the disease before the test results are considered. Thus, a pretest probability of 0.6 means in this case that the physician estimates a 60 percent likelihood of asthma on the basis of all available information but before he sees the test results. The post-test probability (PP) is the likelihood of asthma considering the pretest probability and the test results. The difference between P and PP represents the contribution of the test (which could be helpful or misleading) to the final diagnosis.

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Tistamine and methacholine inhalation challenge are used extensively to determine bronchial reactivity and the likelihood of asthma in patients in whom the diagnosis is not obvious. Critical analyses, however, have shown that, as with all laboratory tests, there is overlap of results for normal and abnormal subjects. This overlap forces the physician to use decision analysis in the interpretation of test results; the analysis may be done subconsciously on the basis of experience and intuition or by a more formal process such as Bayesian analysis. A formal analysis has been published for histamine provocation by Popa and Singleton. To our knowledge an analysis for metha­choline challenge has not been presented, but the recently published data of Casale and associates provide a basis for such an analysis.

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At variance with Pa0₂st and Ve, which tended to return toward normal as a consequence of the pro­gressive recovery of perfusion during the first week or the first month, the P(A-a)0₂, P(a-A)C0₂, and Vd/ Vt%, even after appropriate treatment, showed the persistence of some abnormalities six months later.

The incomplete recovery of perfusion and of some parameters of gas exchange in pulmonary embolism 180 days later may be due in part to the intrinsically sluggish recovery process and in part to the presence of preexisting conditions such as underlying cardiac or pulmonary diseases. In fact, it is known that the response of the pulmonary vascular system to severe pulmonary emboli with time may differ among individuals in relation to age, smoking habit, his­tory of respiratory symptoms, or the presence of respiratory disease.

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The recovery of pulmonary perfusion after embo­lism may be influenced by several factors, such as prompt and adequate treatment, recurrence of em­boli, and underlying pulmonary pathologic abnormal­ities. Therefore, an accurate follow-up of patients, both in the early stages after embolization and later on, is clinically helpful.

Previous reports show that perfusion lung scintigra­phy, owing to its simplicity and safety, still remains the most suitable technique to assess the severity of embolization and to follow the recovery of pul­monary blood flow under treatment. Our data confirm the foregoing reports and, interestingly, show that pulmonary gas exchange and the chest x-ray film may help in this respect.

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