Goals Occupational COPD and Chronic Bronchitis Define COPD and - PDF document

Goals Occupational COPD and Chronic Bronchitis • Define COPD and chronic bronchitis (CB) – epidemiologically and clinically Occupational and Environmental Respiratory Disease • Cover key points in the 2003 ATS statement on COPD and occupation (data through 1999) UCSF March 2016 • Present data from several UCSF COPD studies Paul D. Blanc MD MSPH • Summarize data from other recent studies University of California San Francisco Division of Occupational and Environmental Medicine • Address policy and clinical implications Case History Smoking History • Patient presents at age 68 • Active cigarette smoker, age 14-30 • Progressive dyspnea over 5 years • Maximum of 1½ packs per day • Now short of breath one flight of stairs or with carrying groceries up hill • Quit 40 years previously • No dyspnea at rest; no paroxysmal symptoms • Under 25 pack years total • Occasional wheezing, chest colds; no cough 1

Occupational History Physical Exam • Extremely dusty work (concrete dust) • Thin, but not cachectic • Grinding large concrete display tanks as an • Prolonged expiratory phase exhibit preparatory in an aquarium • No wheezes or rhonchi • Also exposed to epoxies and fiberglass • No ↑ pulmonic component to S2 • Did 6-8 tanks per year x 7 years (1989-94) • No clubbing • Less exposure 1994-1998, then retired Initial Spirometry • Obstruction without reversibility • DLco 59% predicted • DLco/VA 69% predicted • Follow-up PFTs s/p 40 mg prednisone/14 days  no improved airflow 2

While at work: 99mls loss FEV 1 /yr [p<0.01]; After exposure cessation: FEV 1 ∆ NS While at work: FVC ∆ NS; After exposure cessation 109 mls loss FVC/yr [p<0.01] Serial PFTS - Because work was Volume in Liters (FEV 1 , FVC) 5 FVC dusty work, PFTs done at his job 4.5 FEV Flow in Liters Second -1 (FEF 25-75 ) 4 FEF 3.5 3 • 9 serial measurements/11 years 2.5 2 • Gap/6 years 1.5 1 • 12 f/u measurements/9 years 0.5 0 • New measurements include DLco 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 14 DLco/VA Other Data 6 • Serum alpha1anti-trypsin (AIAT) assay 5 4 • Electrophoresis with agarose immuno- fixation 3 DLco/VA 2 • ZZ phenotype 1 0 • Quantified value: 24 units (normal ≥ 90). 2/1/2005 6/1/2005 10/1/2005 2/1/2006 6/1/2006 10/1/2006 2/1/2007 6/1/2007 10/1/2007 2/1/2008 6/1/2008 10/1/2008 2/1/2009 6/1/2009 10/1/2009 2/1/2010 6/1/2010 10/1/2010 2/1/2011 6/1/2011 10/1/2011 2/1/2012 6/1/2012 10/1/2012 2/1/2013 6/1/2013 10/1/2013 2/1/2014 6/1/2014 3

Defining Chronic Obstructive What Diagnosis Does He Have? Pulmonary Disease [COPD] A. Smoking-Related COPD • This is a modern construct B. Alpha-1 Anti-Trypsin Deficiency • It subsumes 3 main disease labels: C. Occupationally-Related COPD D. Emphysema – COPD, Emphysema, Chronic Bronchitis E. All of the Above • Each label is based on different criteria COPD - Diagnosis Role of Cigarette Smoking • Leading risk factor established for COPD • Based on lung function defined by: – Deficit, amount breathed out in 1 second [FEV 1 ] • Accounts for 80% of all cases of disease – And/or its ratio to the total breath [FEV 1 /FVC] • Cut-points use to define COPD vary: • 80%= Population Attributable Risk [PAR%] – FEV 1 /FVC < 0.70 [GOLD Stage I] [also=Population Attributable Fraction, PAF] – FEV 1 /FVC < 0.70 + FEV 1 <80% pred [Gold II] – FEV 1 /FVC < 0.60 [some older studies] – FEV 1 /FVC <90 th %tile Lower Limit Normal • PAF=disease stopped if risk eliminated 4

Impact of Smoking Role Going Beyond Direct Smoking • Primary focus of prevention efforts; minimizing attention to other factors • If direct cigarette smoking doesn’t account – PAF allows overlapping risks [can be >100%] for all COPD cases, what else matters? – Eliminating any risk factor can reduce disease • What is the role of workplace exposures? • Diagnostic impacts – Reluctance to diagnose COPD in nonsmokers • Is there a strong and plausible effect, – Reluctance to diagnose asthma in smokers consistent in multiple studies? ATS Statement • Drafted in 2002, published in 2003; data through 1999 • Reviewed occupational links to asthma and to COPD • Concentrated on population attributable risk (PAR) % / pop attributable fraction (PAF) • Work hazard defined broadly - typically: “exposure to vapors, gas, dust, and fumes” 5

ATS Statement: COPD ATS Statement: Chronic Bronchitis Breathlessness (Effort Dyspnea) • 8 epidemiological studies reviewed • 6 epidemiological studies reviewed including > 38,000 subjects including > 25,000 subjects • U.S. (1987), France (1988), Poland • U.S. (1987), France (1988), Italy (1991), (1990), Italy (1991), Norway (1991), China Norway (1991), China (1993), New (1993), Holland (1994), Spain (1998) Zealand (1997) • PAF for occupational dust/fume: • PAF for occupational dust/fume: Range = 4-24%, Median = 15% Range = 6-30%, Median = 13% ATS Statement: COPD ATS Statement: Conclusion Airflow Obstruction (PFT Deficit) • 6 epidemiological studies reviewed ‘ …occupational exposures account for a including > 12,000 subjects substantial proportion (i.e., from 10-20%) of either symptoms or functional • U.S. (1977,1987), Italy (1991), Norway impairment consistent with COPD…a (1991), Spain (1998), New Zealand (1997) value of 15% is a reasonable estimate of the occupational contribution to the • PAF for occupational dust/fume: population of the burden of COPD. ’ Range = 12-55%, Median = 18% 6

UCSF COPD Study Methods Trupin, Earnest, San Pedro, Balmes, Eisner, Yelin, Katz, Blanc Eur Respir J 2003 22:462-9 • Data from a population-based random digit • Study designed to estimate occupational dial telephone sample, adults aged 55-75 risk for COPD • National USA (48 contiguous states) • Recruit subjects across a wide range of • Over-sampling in regions with higher industries and occupations COPD-related mortality • Define exposure broadly to capture PAR% • Supplemental recruitment of subject- reported MD diagnosis of asthma/COPD • Focus on older age groups at greatest risk Outcomes Definitions Exposure Definitions • Diagnosis: reported physician diagnosis of • Focus on exposure from longest-held job COPD, emphysema, chronic bronchitis • Defined by reported exposure to “vapors, • Diagnosis of asthma also elicited gas, dust, or fumes” [VGDF] • 16 specific exposures elicited: combustion • COPD = COPD or emphysema or chronic byproducts; inorganic, organic dust-fumes bronchitis (+/- asthma) • Also defined by job exposure matrix (JEM) of low, moderate, high likelihood exposure • All analyses adjust for cigarette smoking 7

Figure 1. Telephone Area Codes Corresponding to “Hot Spot” Health Service Figure 2. Recruitment of Study Participants in Three Cohorts Areas with Highest Age-Adjusted COPD Mortality Rates, 1982 - 1993 National Random “Hot Spots” “Hot Spots” Sample Random Sample Condition Sample North Minnesota 17,442 16,042 7,583 Washington Montana Dakota Maine Total contacts Total contacts Total contacts South Wisconsin 207 Dakota VT Oregon Wyoming 802 NH Idaho New MI York MA Iowa Nebraska 814 CT 530 Ohio Pennsylvania Nevada Illinois IN Utah Colorado 740 916 MD NJ RI WV 209 Kansas Missouri 304 2,081 1,850 155 719 DE 559 Kentucky Virginia Potential participants 702 302 Potential participants Potential participants 661 North (with airway condition) 760 Oklahoma Tennessee Arizona Arkansas Carolina New Mexico South 909 Carolina MS Alabama Texas Georgia 850 Louisiana 904 Florida 1,001 (48%) 1,002 (54%) 110 (71%) Interview completed Interview completed Interview completed Figure 3. Specific and Global VGDF VGDF v. 16 Specific Exposures 50% global exp no global exp 45% 40% • Specific exposures ranged from >40% % reporting 35% [indoor engines and diesel exhaust] to 30% 25% < 10% [grain dust and cotton dust] 20% 1 5% 1 0% • The frequency of exposures not captured 5% by VGDF item ranged from 1% to 5% 0% l m g s n i t d t t d t t s s O s s s s s a l o s n s e a u n r u e u u u u t g i a o e e i a v t d a d d d i d s t m l i s f m l g s t o h e n u l n n d o • No single item accounted for substantial a m x a l d r b r W e a o o i o o a r l e a m p m t e b t C r t o C i a r h x r o l G i o W i o e n F E r c o C t I C s A O i l d e added exposure “detection” i S n i D I Specific VGDF Exposure 8

Risk of COPD by Exposure Diagnosis By Exposure Status All COPD and COPD without Chronic Bronchitis UCSF COPD Study: Smoking-VGDF Interactions Principal Conclusions • Between 9-20% (JEM vs. VGDF) of COPD is attributable to occupational exposures • Excluding chronic bronchitis alone, the PAR% ↑ to 14% (JEM) or 31% (VGDF) • There is potential interaction with cigarette smoking exposure 9