Philip J. Roos

Development and testing of the modified version of the Pulmonary Functional Status and Dyspnea Questionnaire (PFSDQ-M)

OBJECTIVE Describe the process of development and testing to reduce the Pulmonary Functional Status and Dyspnea Questionnaire (PFSDQ) from 164 items to a modified questionnaire (the PFSDQ-M) consisting of 40 items. DESIGN Instrument development and testing for reliability, validity, and practicality. SETTING Hospital-based outpatients. PATIENTS Testing was done on three groups of clinically stable patients with chronic obstructive pulmonary disease: a secondary analysis of 131 subjects for item selection, reliability, and validity; 50 additional subjects evaluating the PFSDQ-M for internal consistency, test-retest correlations, and construct validity; and 34 subjects from a longitudinal study for responsiveness. OUTCOME MEASURES PFSDQ, PFSDQ-M, and spirometry. RESULTS The practicality of the PFSDQ-M was supported by its sixth- to seventh-grade reading level, ease of reading (Flesch-Kincaid 69.5), self-administration, brief period for testing (7 minutes initially, 6 minutes on repeated testing), and limited missing data (< 8%). Reliability of the three components was supported by internal consistency alpha = 0.93 for change experienced by the patient with activities (CA), 0.95 for dyspnea with activities (DA), and 0.95 for fatigue with activities (FA). Good stability of the PFSDQ-M was demonstrated on test-retest; r = 0.70 for change, 0.83 for dyspnea, and 0.79 for fatigue (with activities). The usefulness of the PFSDQ-M in discriminating between dyspnea scores in patients based on their rate of deterioration in lung function was demonstrated. CONCLUSIONS The PFSDQ was modified by reducing the number of activities evaluated, standardizing scaling formats, and adding a fatigue component. Findings suggest that the PFSDQ-M demonstrates initial reliability; good validity estimates, as seen with the factor analysis, and the dyspnea and activity scores appear responsive to physiologic changes in lung function over time.

Dyspnea in patients with chronic obstructive pulmonary disease: Does dyspnea worsen longitudinally in the presence of declining lung function? ☆ ☆☆

OBJECTIVE To determine the direction and rate of change in the symptom of dyspnea in patients with chronic obstructive pulmonary disease (COPD) whose lung function has worsened over time. DESIGN Secondary analysis of a longitudinal data set. SETTING Outpatient clinic. PATIENTS Thirty-four medically stable male subjects with chronic obstructive pulmonary disease studied for 5.3 +/- 3.5 years, with a mean reduction in FEV1 over the period studied of 330.9 +/- 288.0 mL. Subjects were 63.3 +/- 5.5 years of age at entry into the study. OUTCOME MEASURES Dyspnea and functional status scores were obtained using the Pulmonary Functional Status and Dyspnea Questionnaire. RESULTS There was no significant difference in reports of dyspnea from the beginning to the end of the study, despite significant reductions in lung function. Of all activities studied, dyspnea when raising arms overhead was the only activity showing a relationship to the slope of change in FEV1 %. CONCLUSION These findings suggest that, although patients with chronic lung disease experience varying degrees of deterioration in lung function longitudinally, there is no evidence that they report worsening of dyspnea in tandem with these physiologic changes. In this study, patient ratings of dyspnea longitudinally were not directly linked to changes in lung impairment.

Valyl-Alanyl-Prolyl-Glycine Serves as a Quantitative Marker for Human Elastins

Abstract Thermolysin digests of human elastins were examined for elastin peptide markers as determined by HPLC followed by amino acid sequencing of promising peaks. The tetrapeptide VAPG was found to occur in the early portion of the chromatogram highly fashion. The peptide appears to be significantly amplified, when compared with the other peptides, in that it is derived from the hexapeptide repeat in e1astin, VGVAPG, which repeats itself in two three-pieceegments in the c-terminal portion of the tropoelastin molecule. VAPG serves as a highly reliable quantitative measure for human elastins, allowing sensitivities to less than a microgram. Thus, it is a significantly more accurate measure than other existing methods. Precision also appears to be enhanced because of the directness of the measurements. The use of VAPG as a quantitative marker for human elastin has clinical application in the study of elastin-based connective tissue diseases.

Extensive alternate exon usage at the 5' end of the sheep tropoelastin gene.

Several overlapping cDNA clones were isolated from a lambda gt10 cDNA library constructed using poly A+ RNA from neonatal sheep lung. DNA sequence analysis of these cDNA recombinants revealed the complete derived amino acid sequence of sheep tropoelastin. A comparison of DNA sequences from individual sheep tropoelastin cDNA also confirmed the presence of several tropoelastin mRNA isoforms in neonatal lung tissue. Coding domains corresponding to exons 13, 14 and 33 were present in several of the sheep tropoelastin cDNA fragments but absent in others. The relative amount of alternate usage of these exons was quantitated by polymerase chain amplification. In confirmation of previous studies in other mammalian species, extensive alternate usage of exon 33 was observed in total RNA isolated from aorta, nuchal ligament and pulmonary artery from neonatal sheep. In striking contrast to all previous studies, however, exons 13 and 14 were shown to be subject to almost the same level of alternate usage as exon 33 in all three neonatal sheep tissues examined.

Quantitation of lung elastin and collagen in protein and essential fatty acid malnourished rats

Thirty-nine 40-day old male Sprague-Dawley rats (average wt. 115g) were divided into 4 groups and fed diets A, control; B, essential fatty acid (EFA) deficient; C, protein deficient; D, combined protein and EFA deficient. At the end of 5 weeks, lungs were removed from the animals for collagen and elastin quantitation and for morphometric measurements. The collagen content of the lungs which ranged from 95-100 micrograms/mg dried fat-free (D.F.F.) tissue, was not altered by protein or EFA deficiencies. The elastin content of lungs was markedly increased in diets C and D while the cross-linking (Isodesmosine-desmosine content) expressed as residues per 1,000 (R/1000) was not different in the four groups. The elastin content of lungs from group D animals was greater than group C suggesting an additive effect from the EFA deficiency in diet D. The morphometric measurements indicated no change in alveolar linear diameter (Lm) while the total alveolar surface area (ISAA1V) was decreased by the deficient diets C and D. The protein deficiency and the combined protein and EFA deficiencies produced an increased elastin content in lung. Elastin cross-linking and collagen quantity was not affected by the dietary treatments. The morphometric measurements indicated that protein deficiency in these animals did not produce structural changes in the lungs as indicated by alveolar dimensions.

Quantitation of Elastin in Tissues and Culture: Problems Related to the Accurate Measurement of Small Amounts of Elastin with Special Emphasis on the Rat

Both rat and sheep elastin can be quantified by measurement of discrete peptides released from the insoluble protein by thermolysin digestion. These peptides are easily visualized and measured by HPLC. With the sheep the tallest peak on the chromatogram represents the VGVPG pentapeptide derived from a repeating sequence seen in elastin from many species. This repeating sequence allows for amplification of the signal significantly above background so that accurate quantitation can be carried out. The measurement is reproducible over a wide range of protein concentrations. With the rat however the pentapeptide is not present but appears to be replaced by other repeating sequences. We quantitated and determined amino acid sequence on 8 peaks present in the early portion of the chromatogram for purposes of quantifying rat elastin. That signal most reliably present over a range of concentrations was tyrosyl-glycine (YG) which eluted at 8.5 minutes. We have used YG as a basis for quantitation of rat elastin both from tissues and tissue culture. We have also shown that the desmosine crosslinks are not constant in elastin produced in a neonatal rat smooth muscle culture system but vary with the age of the culture. We thus propose that an index of maturation be considered for a given elastin in the form of mumoles of crosslink per gram of elastin so as to better define its quality.