An isolated reduction of the FEV3/FVC ratio is an indicator of mild lung injury.

BACKGROUND: The FEV3/FVC ratio is not discussed in the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines for lung function interpretation in spite of narrow confidence limits of normal and its association with smoking. We sought to determine whether a reduction in only the FEV3/FVC ratio was associated with physiologic changes compared with subjects with normal FEV1/FVC and FEV3/FVC ratios. METHODS: Lung volumes and diffusion were studied in individuals with concomitant spirometry. Patients with restriction on total lung capacity (TLC) were excluded, as were repeat tests on the same patient. A total of 13,302 subjects were divided into three groups: (1) normal FEV1/FVC and FEV3/FVC (n = 7,937); (2) only a reduced FEV3/FVC (n = 840); and (3) reduced FEV1/FVC (n = 4,525). RESULTS: Subjects with only a reduced FEV3/FVC compared with those with normal FEV1/FVC and FEV3/FVC ratios had higher mean % predicted TLC (99.1% vs 97.1%, P < .001), residual volume (RV) (109.4% vs 102.3%, P < .001), and RV/TLC ratio (110.1% vs 105.4%, P < .001). They had lower mean % predicted FEV1 (82.6% vs 90.2%, P < .001), inspiratory capacity (94.5% vs 98.2%, P < .001), and diffusing capacity of lung for carbon monoxide (Dlco) (78.3% vs 81.9%, P < .001). Their mean BMI was lower (30.8 vs 31.5, P < .005), they were older (61.2 vs 57.2, P < .001), and more likely male (52.0% vs 40.4%, P < .001), with no racial differences. Comparing this group to those with a reduced FEV1/FVC, similar but greater differences were noted in all of the previous measurements, though mean age and sex were not significantly different. CONCLUSIONS: The FEV3/FVC ratio should be routinely reported on spirometry. An isolated reduction may indicate an early injury pattern of hyperinflation, air trapping, and loss of Dlco.

The diagnostic importance of a reduced FEV1/FEV6.

BACKGROUND: On spirometry the FEV(1)/FEV(6) ratio has been advocated as a surrogate for the FEV(1)/FVC. The significance of isolated reductions in either the FEV(1)/FEV(6) or FEV(1)/FVC is not known. METHODS: First-time adult spirograms (n = 22,837), with concomitant lung volumes (n = 12,040), diffusion (n = 14,154), and inspiratory capacity (n = 12,480) were studied. Four groups were compared. 1) Only FEV(1)/FEV(6) reduced (n = 302). 2) Only FEV(1)/FVC reduced (n = 1158). 3) Both ratios reduced (n = 6593). 4) Both ratios normal (n = 14,784). RESULTS: In patients with obstructed spirometry (either a reduced FEV(1)/FVC and/or FEV(1)/FEV(6)), 3.8% only had a reduced FEV(1)/FEV(6), while 14.4% only had a reduced FEV(1)/FVC. The mean FEV(1) was lower when both ratios were reduced. The group with only a reduced FEV(1)/FEV(6), compared to only the FEV(1)/FVC reduced, had a lower FEV(1), FVC, BMI, Expiratory Time, and IC (p values < 0.0001). DL(CO) was also lower (p = 0.005), and the FEV(1)/FVC and RV/TLC were higher (p values < 0.0001). When the patients with only a reduced FEV(1)/FEV(6) had a subsequent spirogram, 60% had a reduced FEV(1)/FVC when their mean expiratory times were 3.5 seconds longer. Ninety percent of this group had strong clinical evidence of airways obstruction. CONCLUSIONS: The FEV(1)/FEV(6) is not as sensitive as the FEV(1)/FVC for diagnosing airways obstruction, but in the presence of a normal FEV(1)/FVC, subjects have greater physiologic abnormalities than when only the FEV(1)/FVC is reduced. The FEV(1)/FEV(6) ratio should not replace the FEV(1)/FVC as the standard for airways obstruction, but there is benefit including this measurement to identify individuals with greater air trapping and diffusion abnormalities.

Using spirometry to rule out restriction in patients with concomitant low forced vital capacity and obstructive pattern.

BACKGROUND: Different formulas have been proposed to exclude restriction based on spirometry, however none of them have specifically tested the patients whose spirometry show both obstruction and a low forced vital capacity (FVC). STUDY OBJECTIVE: The study was designed to create an algorithm that would better predict the absence of restriction in such patients. DESIGN: Retrospective analysis of prospectively collected data. METHODS: A cohort of consecutive adults that underwent complete pulmonary function testing from 2002-2004 was analyzed. The data was randomly split into two groups to allow for derivation and then validation of a predictive formula. Patients were randomly assigned into either a "derivation" or "validation" group. In the derivation group, stepwise logistic regression was used to determine a formula and optimal cut-off value for the variable with the best discriminative capacity. The formula was applied subsequently to the validation group to test the results and compared to previously published formula. RESULTS: The study group contained 766 patients. We determined that the variable with the highest association with TLC was [(FEV(1)/FVC) % predicted/FVC % predicted]. A value of ≥1.11 was found to be the maximal cutoff to predict the absence of restriction. The formula was applied to a validation group (n=397) and performed better than prior published algorithm with a sensitivity, specificity, positive predictive value and negative predictive value of 95%, 44%, 22%, and 98%, respectively. CONCLUSION: Our formula performs superior to the previously published algorithms in patients with concomitant low FVC and obstruction to exclude restriction.

Two ATS recommended protocols for administration of methacholine are not equal.

BACKGROUND: The 1999 American Thoracic Society methacholine challenge guidelines stated that the 5-breath dosimeter method of methacholine administration is similar to the 2-minute tidal breath method. Recent data has disputed this assertion. We examined the differences in the diagnosis of asthma using these two methods. METHODS: Data were abstracted from a prospectively generated pulmonary function database over 4 years. During the first 2 years the 5-breath dosimeter method was used, and the subsequent 2 years the 2-minute tidal breath method was used. The effect of the delivery technique was assessed by crude and adjusted odds ratios, controlling for known confounders and group differences. RESULTS: A total of 907 subjects underwent methacholine challenge testing during the 4-year study period: 19.3% of the subjects tested with the 5-breath dosimeter method and 31.2% of those tested with the 2-minute tidal breathing method had a PC20 16.0 mg/mL) was also altered by the differences between the testing techniques. Using the 5-breath dosimeter method, 72.4% of subjects were ruled out for airway hyper-responsiveness, whereas only 59.9% of subjects were ruled out with the 2-minute tidal breathing technique (p < 0.001). CONCLUSION: The two recommended protocols for the diagnosis of asthma are not equivalent and significantly alter the rate of diagnosis of asthma as well as the severity. The differences were seen across all PC20 levels, from those with strongly positive tests (PC20 16.0 mg/mL).

Specific conductance criteria for a positive methacholine challenge test: are the American Thoracic Society guidelines rather generous?

BACKGROUND: American Thoracic Society (ATS) guidelines for methacholine challenge testing (MCT) discuss specific airways conductance (sG(aw)) as a surrogate marker for forced expiratory volume in the first second (FEV(1)) to diagnose airways obstruction. The guidelines suggest a cutoff value of 45% drop in sG(aw) to diagnose a positive MCT. However, there is no available evidence that supports this cutoff value of 45%. We conducted this study to examine the relationship between FEV(1) and sG(aw) during MCT. METHODS: One-hundred thirty-eight patients who had both sG(aw) and FEV(1) measured during MCT between April 2003 and March 2004 were retrospectively evaluated. The tests were done according to the ATS guidelines. Data were first analyzed using linear regression modeling, comparing the change in FEV(1) to changes in sG(aw). Then the sensitivity and specificity were generated for different cut points, using receiver operating characteristic analysis. RESULTS: Thirty-eight patients had a positive MCT based on ATS FEV(1) criteria. A decrease of 20% in FEV(1) correlated with a drop of 56% in sG(aw) (95% confidence interval 52% to 60%, r(2) 0.35, P < .001). Using 20% decline from baseline in FEV(1) at different PC(20) (provocational concentration that produced a > or = 20% FEV(1) decrease) values (4 mg/mL, 8 mg/mL, and 16 mg/mL), we then analyzed the sensitivity, specificity, positive predictive value, and negative predictive value of the 45% decline in sG(aw) and compared it with a 56% decline in sG(aw). Using receiver operating characteristic analysis, we were able to find that a cutoff of 51-52% performed better than either of the 2 values. CONCLUSIONS: Our study suggests that the ATS suggested cutoff value of 45% decline in sG(aw) to diagnose a positive MCT may be rather generous, and a decline of 51% from baseline may provide a more accurate measure of airway hyper-responsiveness. Further studies using well defined subjects with and without asthma should be done to better assess the test characteristics of sG(aw).

Predictive value of sGaw, FEF(25-75), and FEV1 for development of asthma after a negative methacholine challenge test.

BACKGROUND: A 20% change in forced expiratory volume in 1 second (FEV(1)) during methacholine challenge testing (MCT) is a reliable marker of asthma. When the FEV(1) decrease is < 20%, there is controversy whether other changes in flows and conductance may be useful. We conducted this study to determine whether changes in sGaw, FEF(25 - 75), and FEV(1) in a negative MCT could predict future occurrence of asthma over a 3-year period. METHODS: A total of 100 consecutive patients with clinical suspicion of asthma but who had a negative MCT per ATS FEV(1) criteria (< 20% FEV(1) decline at 16 mg/mL of methacholine) performed by the 5-breath dosimeter method were analyzed. Two pulmonary fellows, blinded to MCT results, reviewed the patients' medical records. Patients were classified into one of three categories: asthmatic, unclear, and not asthmatic. Decreases in sGaw, FEF(25 - 75), and FEV(1) in the five groups were then retrieved. Analysis of variance (ANOVA) was used for data analysis. RESULTS: Of 100 patients, 23 were excluded owing to lack of a 3-year follow-up. After complete data review, the number of patients (n) in each group was as follows: asthmatic (n = 15), unclear (n = 7), and not asthmatic (n = 55). sGaw and FEF(25 - 75) decreases from the negative MCT could not predict asthma; however, decreases in FEV(1) were associated with future asthma occurrence (sGaw p = 0.21, FEF25-75 p = 0.07, FEV(1) p = 0.0009). Forty-three percent of the patients who had a 10% to 20% decline in FEV(1) eventually developed asthma. CONCLUSION: Up to 20% of patients who have symptoms suggestive of asthma but a negative MCT can still develop asthma. Declines in sGaw and FEF(25 - 75) in a negative MCT appear to have no clinical significance. A decrease in FEV(1), especially 10% to 20%, is associated with the diagnosis of future asthma.