PMID- 16284217 OWN - NLM STAT- MEDLINE DCOM- 20060214 LR - 20190108 IS - 0040-6376 (Print) IS - 1468-3296 (Electronic) IS - 0040-6376 (Linking) VI - 61 IP - 2 DP - 2006 Feb TI - Neutrophilic inflammation and IL-8 levels in induced sputum of alpha-1-antitrypsin PiMZ subjects. PG - 129-33 AB - 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. FAU - Malerba, M AU - Malerba M AD - Department of Internal Medicine, University of Brescia, 1st Divisione di Medicina, Spedali Civili, Piazza Spedali Civili 1, 25100 Brescia, Italy. malerba@master.cci.unibs.it FAU - Ricciardolo, F AU - Ricciardolo F FAU - Radaeli, A AU - Radaeli A FAU - Torregiani, C AU - Torregiani C FAU - Ceriani, L AU - Ceriani L FAU - Mori, E AU - Mori E FAU - Bontempelli, M AU - Bontempelli M FAU - Tantucci, C AU - Tantucci C FAU - Grassi, V AU - Grassi V LA - eng PT - Journal Article DEP - 20051111 PL - England TA - Thorax JT - Thorax JID - 0417353 RN - 0 (Interleukin-8) RN - 1HGW4DR56D (Leukotriene B4) RN - 7U1EE4V452 (Carbon Monoxide) SB - IM MH - Aged MH - Bronchitis/*metabolism/pathology MH - Carbon Monoxide/metabolism MH - Case-Control Studies MH - Female MH - Forced Expiratory Volume/physiology MH - Humans MH - Interleukin-8/*metabolism MH - Leukotriene B4/*metabolism MH - Male MH - Middle Aged MH - Neutrophils/pathology MH - Sputum/cytology MH - Vital Capacity/physiology MH - alpha 1-Antitrypsin Deficiency/*metabolism/pathology/physiopathology PMC - PMC2104580 COIS- Conflict of interest: none declared. EDAT- 2005/11/15 09:00 MHDA- 2006/02/16 09:00 PMCR- 2009/02/01 CRDT- 2005/11/15 09:00 PHST- 2005/11/15 09:00 [pubmed] PHST- 2006/02/16 09:00 [medline] PHST- 2005/11/15 09:00 [entrez] PHST- 2009/02/01 00:00 [pmc-release] AID - thx.2005.043471 [pii] AID - tx43471 [pii] AID - 10.1136/thx.2005.043471 [doi] PST - ppublish SO - Thorax. 2006 Feb;61(2):129-33. doi: 10.1136/thx.2005.043471. Epub 2005 Nov 11.