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.

Factors predicting inhaled corticosteroid responsiveness in African American patients with asthma.

BACKGROUND: African American patients disproportionately experience uncontrolled asthma. Treatment with an inhaled corticosteroid (ICS) is considered first-line therapy for persistent asthma. OBJECTIVE: We sought to determine the degree to which African American patients respond to ICS medication and whether the level of response is influenced by other factors, including genetic ancestry. METHODS: Patients aged 12 to 56 years who received care from a large health system in southeast Michigan and who resided in Detroit were recruited to participate if they had a diagnosis of asthma. Patients were treated with 6 weeks of inhaled beclomethasone dipropionate, and pulmonary function was remeasured after treatment. Ancestry was determined by genotyping ancestry-informative markers. The main outcome measure was ICS responsiveness defined as the change in prebronchodilator FEV(1) over the 6-week course of treatment. RESULTS: Among 147 participating African American patients with asthma, average improvement in FEV(1) after 6 weeks of ICS treatment was 11.6%. The mean proportion of African ancestry in this group was 78.4%. The degree of baseline bronchodilator reversibility was the only factor consistently associated with ICS responsiveness, as measured by both an improvement in FEV(1) and patient-reported asthma control (P = .001 and P = .021, respectively). The proportion of African ancestry was not significantly associated with ICS responsiveness. CONCLUSIONS: Although baseline pulmonary function parameters appear to be associated with the likelihood to respond to ICS treatment, the proportion of genetic African ancestry does not. This study suggests that genetic ancestry might not contribute to differences in ICS controller response among African American patients with asthma.

Calcium and vitamin D in sarcoidosis: how to assess and manage.

The synthesis of vitamin D is altered by the granulomatous inflammation of sarcoidosis leading to increased production of 1, 25-dihydroxyvitamin D. Mounting evidence suggests that vitamin D is an immunomodulating hormone that inhibits both antigen presentation by cells of the innate immune system, and the cytokine release and proliferation of Th1 cells. These and other extraskeletal health benefits have led to an increase in vitamin D assessment and pharmacological supplementation in the general population. This review highlights the altered synthesis and general immunomodulating properties of vitamin D with a special emphasis on known interactions with sarcoidosis. In addition, the assessment of vitamin D nutritional status, its pharmacological supplementation, and the management of bone health in patients with sarcoidosis are reviewed.

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).

Racial differences in sarcoidosis granuloma density.

STUDY OBJECTIVES: While sarcoidosis generally inflicts a greater morbidity on African-American compared with Caucasian patients, no studies have examined whether racial differences exist in the intensity of the histologic hallmark of sarcoidosis, noncaseating granulomas. DESIGN AND SETTING: The study was conducted as a retrospective case series in a tertiary referral center. PATIENTS: The study included 187 patients with histopathologic confirmation of sarcoidosis by trans- and/or endobronchial biopsy between July 1991 and December 2001. MEASUREMENTS AND RESULTS: Granuloma density was the average number of granulomas per biopsy piece on the slide with the most intense granulomatous inflammation at fourfold magnification. Overall, African-American patients had a twofold greater median granuloma density than Caucasians (p = 0.005). In a negative binomial multivariate model, radiographic pattern had the strongest association with granuloma density, with Scadding stage II and III patients having adjusted granuloma densities of 60% (p = 0.005) and 105% (p = 0.0001) higher than stage I patients. In the specific-tissue types, radiographic stage-adjusted granuloma densities in African-American patients were 49% greater in bronchial tissue (p = 0.03), but only a 27% greater in alveolar tissue (p = 0.51). CONCLUSIONS: A greater granuloma density in bronchiolar lung tissue of African-American sarcoidosis patients may explain racial differences in diagnostic yield by lung biopsy and disease severity at diagnosis. This association persists even after controlling for Scadding radiographic stage, a measure of disease severity strongly associated with granuloma density.