title: Human diaphragm remodeling associated with chronic obstructive pulmonary disease: clinical implications.
abstract: Diaphragm remodeling associated with chronic obstructive pulmonary disease (COPD) consists of a fast-to-slow fiber type transformation as well as adaptations within each fiber type. To try to explain disparate findings in the literature regarding the relationship between fiber type proportions and FEV1, we obtained costal diaphragm biopsies on 40 subjects whose FEV1 ranged from 118 to 16% of the predicted normal value. First, we noted that our exponential regression model indicated that changes in FEV1 can account for 72% of the variation in the proportion of Type I fibers. Second, to assess the impact of COPD on diaphragm force generation, we measured maximal specific force generated by single permeabilized fibers prepared from the diaphragms of two patients with normal pulmonary function tests and two patients with severe COPD. We noted that fibers prepared from the diaphragms of severe COPD patients generated a lower specific force than control fibers (p < 0.001) and Type I fibers generated a lower specific force than Type II fibers (p < 0.001). Our finding of an exponential relationship between the proportion of Type I fibers and FEV1 accounts for discrepancies in the literature. Moreover, our single-fiber results suggest that COPD-associated diaphragm remodeling decreases diaphragmatic force generation by adaptations within each fiber type as well as by fiber type transformations.
authors.affiliation: Philadelphia Veterans Affairs Medical Center, Pennsylvania, USA. sdlevine@mail.med.upenn.edu
authors.forename: Sanford
authors.initials: S
authors.lastname: Levine
authors.forename: Taitan
authors.initials: T
authors.lastname: Nguyen
authors.forename: Larry R
authors.initials: LR
authors.lastname: Kaiser
authors.forename: Neal A
authors.initials: NA
authors.lastname: Rubinstein
authors.forename: Greg
authors.initials: G
authors.lastname: Maislin
authors.forename: Christopher
authors.initials: C
authors.lastname: Gregory
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Rome
authors.forename: Gary A
authors.initials: GA
authors.lastname: Dudley
authors.forename: Gary C
authors.initials: GC
authors.lastname: Sieck
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Shrager
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001707:Biopsy, Needle; D015331:Cohort Studies; D003964:Diaphragm / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007150:Immunohistochemistry; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology*; D011336:Probability; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis*; D015656:Respiratory Mechanics / Q000502:physiology; D012720:Severity of Illness Index; D013147:Spirometry; D014109:Total Lung Capacity