The impact of cigarette smoke (CS), a risk factor for rheumatoid arthritis (RA), on autoantibody production was studied in humans and mice with and without chronic lung disease (LD). Rheumatoid factor (RF), anti-cyclic citrullinated peptides (CCPs), and anti-HSP70 autoantibodies were measured in several mouse strains and in cohorts of smokers and nonsmokers with and without autoimmune disease. Chronic smoking-induced RFs in AKR/J mice, which are most susceptible to LD. RFs were identified in human smokers, preferentially in those with LD. Anti-HSP70 autoantibodies were identified in CS-exposed AKR/J mice but not in ambient air exposed AKR/J controls. Whereas inflammation could induce anti-HSP70 IgM, smoke exposure promoted the switch to anti-HSP70 IgG autoantibodies. Elevated anti-CCP autoantibodies were not detected in CS-exposed mice or smokers. AKR/J splenocytes stimulated in vitro by immune complexes (ICs) of HSP70/anti-HSP70 antibodies produced RFs. The CD91 scavenger pathway was required as anti-CD91 blocked the HSP70-IC-induced RF response. Blocking Toll-like receptors did not influence the HSP70-IC-induced RFs. These studies identify both anti-HSP70 and RFs as serological markers of smoke-related LD in humans and mice. Identification of these autoantibodies could suggest a common environmental insult, namely CS, in a number of different disease settings.Keywords: Autoantibodies r Heat shock protein 70 r Lung disease r Rheumatoid factor IntroductionSmoking is a very strong environmental risk factor that is linked to rheumatoid arthritis (RA) [1,2] and other autoimmune disCorrespondence: Dr. Marianna M. Newkirk e-mail: Marianna.newkirk@mcgill.ca eases [3][4][5]. Furthermore, there is little information on the association between the most common smoke-induced lung disease (LD), chronic obstructive pulmonary disease (COPD), and serological markers associated with autoimmunity.In North American Native (NAN) populations the prevalence of RA can be three times that of Caucasians [6]. Whereas smoking rates have decreased in the past decade in Caucasians, with 18% of Canadians >15 years of age smoking, 60-70% C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu1052 Marianna M. Newkirk et al. Eur. J. Immunol. 2012. 42: 1051-1061 of NANs (residing mostly on reservations) smoke (Health Canada). Although smoking cessation can lower RA risk and disease burden, the risk continues 10 years after cessation [1] and similarly, prolonged smoking cessation is critical for the reduction of lung cancer [7]. Lung inflammation, oxidative stress, and protease burden remain elevated for several months after smoking cessation [8]. Early diagnosis of those at risk of smoking-related diseases ideally by the use of informative biomarkers is critical with sustained cessation an important goal. Rheumatoid factor (RF), used in the diagnosis of RA [9], is an autoantibody of any isotype that binds IgG Fc. Epidemiological studies have shown that RF-positive RA patients are most associated with an increased risk conferred f...

CLINICIAN’S CAPSULEWhat is known about the topic?Transport of STEMI patients directly to the cath lab (STEMI bypass) by advanced care paramedics (ACPs) is common practice. The safety of this practice with primary care paramedics (PCPs) is unknown.What did this study ask?What is the prevalence and breakdown of events during PCP STEMI bypass?What did this study find?Clinically important events are common in STEMI bypass patients. A smaller proportion of events would be addressed differently by ACP compared to PCP protocols.Why does this study matter to clinicians?This study adds to the evidence that PCP STEMI bypass is safe.

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Introduction: In Ottawa, STEMI patients are transported directly to percutaneous coronary intervention (PCI) by advanced care paramedics (ACPs), primary care paramedics (PCPs), or transferred from PCP to ACP crew (ACP-intercept). PCPs have a limited skill set to address complications during transport.The objective of this study was to determine what clinically important events (CIEs) occurred in STEMI patients transported for primary PCI via a PCP crew, and what proportion of such events could only be treated by ACP protocols. Methods: We conducted a health record review of STEMI patients transported for primary PCI from Jan 1, 2011-Dec 21, 2015. Ottawa has a single PCI center and its EMS system employs both PCP and ACP paramedics. We identified consecutive STEMI bypass patients transported by PCP-only and ACP-intercept using the dispatch database. A data extraction form was piloted and used to extract patient demographics, transport times, and primary outcomes: CIEs and interventions performed during transport, and secondary outcomes: hospital diagnosis, and mortality. CIEs were reviewed by two investigators to determine if they would be treated differently by ACP protocols. We present descriptive statistics. Results: We identified 967 STEMI bypass cases among which 214 (118 PCP-only and 96 ACP-intercept) met all inclusion criteria. Characteristics were: mean age 61.4 years, 78% male, 31.8% anterior and 44.4% inferior infarcts, mean response time 6 min, total paramedic contact time 29 min, and in cases of ACP-intercept 7 min of PCP-only contact time.A CIE occurred in 127 (59%) of cases: SBP<90 mmHg 26.2%, HR<60 30.4%, HR>100 20.6%, malignant arrhythmias 7.5%, altered mental status 6.5%, airway intervention 2.3%, 2 patients (0.9%) arrested, both survived. Of the CIE identified, 54 (42.5%) could be addressed differently by ACP vs PCP protocols (25.2% of total cases). The majority related to fluid boluses for hypotension (44 cases; 35% of CIE). ACP intervention for CIEs within the ACP intercept group was 51.6%. There were 6 in-hospital deaths (2.8%) with no difference in transport crew type. Conclusion: CIEs are common in STEMI bypass patients however a smaller proportion of such CIE would be addressed differently by ACP protocols compared to PCP protocols. The vast majority of CIE appeared to be transient and of limited clinical significance.