BACKGROUND: Severe alpha-1-antitrypsin deficiency (AATD), due to homozygosity for the protease inhibitor (Pi) Z allele, is a genetic risk factor for chronic obstructive pulmonary disease (COPD). In a previous study the sputum of severe AATD subjects with airflow obstruction showed a pattern of cellular inflammation similar to COPD patients. It is uncertain whether heterozygotes for the Z allele or intermediate deficiency (PiMZ) have an increased risk of developing COPD. METHODS: Sputum cell counts and the supernatant level of the neutrophil chemoattractant interleukin (IL)-8 were investigated by sputum induction in 10 non-smoker asymptomatic PiMZ subjects with normal pulmonary function, 10 patients with stable COPD, and 10 age matched normal subjects. Data are expressed as mean (SD). RESULTS: The mean (SD) number of neutrophils was significantly higher (p<0.01) in the sputum of PiMZ subjects (84.5 (22.2) x10(4)/ml) and patients with COPD (126.9 (18.8) x10(4)/ml) than in matched normal subjects (55.0 (8.7) x10(4)/ml). IL-8 levels were increased in PiMZ subjects (828.5 (490.6) ng/ml; median 1003.0 ng/ml; range 1260-100 ng/ml) and in COPD patients (882.5 (524.3) ng/ml; median 934.9 ng/ml; range 1506-258 mg/ml) compared with normal subjects (3.5 (0.5) ng/ml; median 3.5 ng/ml; range 4.5-2.5 ng/ml). There was a significant positive correlation between IL-8 supernatant concentration and neutrophil count in PiMZ subjects (p = 0.036; r = 0.66). An inverse correlation was observed between the percentage of neutrophils and forced expiratory volume in 1 second (% predicted) in patients with COPD (p = 0.04; r = -0.43). CONCLUSIONS: These findings indicate that PiMZ subjects without airflow obstruction may have an IL-8 related neutrophilic inflammation in the airways, similar to stable COPD patients, suggesting an increased risk of developing pulmonary changes.
BACKGROUND: Severe alpha-1-antitrypsin deficiency (AATD), due to homozygosity for the protease inhibitor (Pi) Z allele, is a genetic risk factor for chronic obstructive pulmonary disease (COPD). In a previous study the sputum of severe AATD subjects with airflow obstruction showed a pattern of cellular inflammation similar to COPDpatients. It is uncertain whether heterozygotes for the Z allele or intermediate deficiency (PiMZ) have an increased risk of developing COPD. METHODS: Sputum cell counts and the supernatant level of the neutrophil chemoattractant interleukin (IL)-8 were investigated by sputum induction in 10 non-smoker asymptomatic PiMZ subjects with normal pulmonary function, 10 patients with stable COPD, and 10 age matched normal subjects. Data are expressed as mean (SD). RESULTS: The mean (SD) number of neutrophils was significantly higher (p<0.01) in the sputum of PiMZ subjects (84.5 (22.2) x10(4)/ml) and patients with COPD (126.9 (18.8) x10(4)/ml) than in matched normal subjects (55.0 (8.7) x10(4)/ml). IL-8 levels were increased in PiMZ subjects (828.5 (490.6) ng/ml; median 1003.0 ng/ml; range 1260-100 ng/ml) and in COPDpatients (882.5 (524.3) ng/ml; median 934.9 ng/ml; range 1506-258 mg/ml) compared with normal subjects (3.5 (0.5) ng/ml; median 3.5 ng/ml; range 4.5-2.5 ng/ml). There was a significant positive correlation between IL-8 supernatant concentration and neutrophil count in PiMZ subjects (p = 0.036; r = 0.66). An inverse correlation was observed between the percentage of neutrophils and forced expiratory volume in 1 second (% predicted) in patients with COPD (p = 0.04; r = -0.43). CONCLUSIONS: These findings indicate that PiMZ subjects without airflow obstruction may have an IL-8 related neutrophilic inflammation in the airways, similar to stable COPDpatients, suggesting an increased risk of developing pulmonary changes.
Authors: J V Fahy; H A Boushey; S C Lazarus; E A Mauger; R M Cherniack; V M Chinchilli; T J Craig; J M Drazen; J G Ford; J E Fish; E Israel; M Kraft; R F Lemanske; R J Martin; D McLean; S P Peters; C Sorkness; S J Szefler Journal: Am J Respir Crit Care Med Date: 2001-05 Impact factor: 21.405
Authors: Ravi Mahadeva; Carl Atkinson; Zhenjun Li; Susan Stewart; Sabina Janciauskiene; Diane G Kelley; Jasvir Parmar; Rebecca Pitman; Steven D Shapiro; David A Lomas Journal: Am J Pathol Date: 2005-02 Impact factor: 4.307
Authors: P Marco Fisichella; Christopher S Davis; Erin Lowery; Luis Ramirez; Richard L Gamelli; Elizabeth J Kovacs Journal: J Am Coll Surg Date: 2013-04-28 Impact factor: 6.113
Authors: D W Russell; M Hardison; K R Genschmer; T Szul; P E Bratcher; M Abdul Roda; X Xu; L Viera; J E Blalock; A Gaggar; B D Noerager Journal: Biochem Biophys Res Commun Date: 2019-08-07 Impact factor: 3.575
Authors: O Guttman; B M Baranovski; R Schuster; Z Kaner; G S Freixo-Lima; N Bahar; N Kalay; M I Mizrahi; I Brami; D E Ochayon; E C Lewis Journal: Clin Exp Immunol Date: 2015-02 Impact factor: 4.330
Authors: David A Bergin; Emer P Reeves; Paula Meleady; Michael Henry; Oliver J McElvaney; Tomás P Carroll; Claire Condron; Sanjay H Chotirmall; Martin Clynes; Shane J O'Neill; Noel G McElvaney Journal: J Clin Invest Date: 2010-11-08 Impact factor: 14.808
Authors: Auyon J Ghosh; Brian D Hobbs; Matthew Moll; Aabida Saferali; Adel Boueiz; Jeong H Yun; Frank Sciurba; Lucas Barwick; Andrew H Limper; Kevin Flaherty; Gerard Criner; Kevin K Brown; Robert Wise; Fernando J Martinez; David Lomas; Peter J Castaldi; Vincent J Carey; Dawn L DeMeo; Michael H Cho; Edwin K Silverman; Craig P Hersh Journal: Am J Respir Crit Care Med Date: 2022-02-01 Impact factor: 21.405
Authors: Eli C Lewis; Mark Mizrahi; Michel Toledano; Nathaniel Defelice; Joanne L Wright; Andrew Churg; Leland Shapiro; Charles A Dinarello Journal: Proc Natl Acad Sci U S A Date: 2008-10-13 Impact factor: 11.205
Authors: Kevin Molloy; Craig P Hersh; Valerie B Morris; Tomás P Carroll; Catherine A O'Connor; Jessica A Lasky-Su; Catherine M Greene; Shane J O'Neill; Edwin K Silverman; Noel G McElvaney Journal: Am J Respir Crit Care Med Date: 2014-02-15 Impact factor: 21.405