Lung Toxicity - 4A: Restrictive lung disease
• restrictive lung disease
– chronic lung disease characterized by progressive stiffening of lung parenchyma – arising from chronic localized inflammation followed by pulmonary fibrosis – scarring and destruction of alveoli and terminal airways --> loss of vital capacity
• localized inflammation
– principally parenchymal tissue (nodular, arborized, „ground glass‟ on Xrays)
• alveoli + adjacent respiratory bronchioles (RB) and membranous bronchioles (MB)
– no large airway involvement (no bronchial thickening on Xrays)
• pulmonary fibrosis
– localized chronic inflammation and scarring in alveoli and terminal airways – pathological formation of fibrous scar tissue (mainly collagen fibres) – fibrosis in alveolar walls (parenchymal disease)
• interstitial fibrosis (alveolar interstitium)
– alveolar capillary destruction
F2007 HLTH 350 Lecture 4A 1
Lung abnormalities in restrictive lung disease
• reduced lung compliance
– interstitial fibrosis -- middle layer of alveolar wall thickens and scars – abnormal stiffness in alveolar walls – greater effort required to inflate lungs
• reduction in total lung (alveolar) capacity (TLC)
– progressive reduction in forced vital capacity (FVC) in spirometric tests
• loss of functional alveoli (and some small airways)
• reduced gas exchange
– due to interstitial thickening and scarring of alveolar walls – destruction of alveolar capillaries
• alveolar capillary block and cor pulmonale (advanced disease)
F2007 HLTH 350 Lecture 4A 2
Spirometry testing in restrictive lung diseases
• reduced FVC
– reduced capacity for lungs to fill with air at inspiration – major diagnostic feature of restrictive lung diseases
• FEV1 may be unaffected or moderately reduced
– depends on extent of small airways disease
• FEV1/FVC ratio may be in ‘normal’ range or elevated
– opposite pattern to obstructive lung diseases
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Classes of interstitial lung disease
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Mineral dust disease - pneumoconiosis
• pneumoconiosis (‘dust in the lungs’ -Grk.)
– – – – – – – – accumulation of large quantities of mineral dust in lungs chronic restrictive lung disease long latency (years or decades) variable in occurrence and severity between individuals and groups „hard rock‟ mining -- gold, uranium, nickel, zinc, other metal ores quarrying of granite and other igneous rocks tunneling and other excavations coal mining
• dusty occupations long associated with chronic lung disease
• degenerative lung disease after years of exposure
– “miner‟s consumption” -- combination of lung degeneration assoc with TB
• may overlap with some obstructive lung pathology, esp. in smokers
– need to distinguish clinically between pneumoconiosis vs. COPD
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Workplace mineral dusts and metals associated with pneumoconiosis
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Sources of variability in mineral dust diseases
• lung infection
– often made workers more vulnerable to tuberculosis – still prevalent in developing countries e.g. South African gold miners – is it pneumoconiosis or is it TB?
• smoking history
– most miners have a history of past or current cigarette smoking – is it pneumoconiosis or is it COPD?
• particle factors
– size, shape, hygroscopicity, persistence in lung, etc. – respirable fraction
• defines what fraction of inhalable dust (<10 uM) is respirable dust (<5 or 2.5 uM) • RF = PM5/PM10 (or PM2.5 / PM10) • only respirable fraction of mineral dusts are deemed hazardous
– example: WTC dust Sept 11 RF = .02 ( i.e. 2%)
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Classes of mineral dust
• „benign’ (inert) dusts
– most common mineral dusts appear harmless to lungs – appear to cause minimal or no lung inflammation – considered as “nuisance dusts‟
• fibrogenic (toxic) dusts
– relatively small exposures cause severe pulmonary fibrosis – can induce severe parenchymal inflammation – only a few mineral dusts are fibrogenic -- silica, asbestos
• variable (mixed) dusts
– coal dusts (varying widely in silica content)
• PNOC
– Particulates Not Otherwise Classified – replaces obsolete terms such as nuisance dusts, benign dusts etc.
F2007 HLTH 350 Lecture 4A 8
PNOC - Particulates Not Otherwise Classified
• American Conference of Government Industrial Hygienists (ACGIH)
– devised term in 1994; also used by many government regulatory bodies
• PNOR - Particulates Not Otherwise Regulated (U.S. OSHA)
• refers to occupational dusts with no evidence of specific toxic effects
– architecture of air spaces (alveoli) remains intact – collagen (scar tissue) not formed to a significant extent – tissue (inflammatory) reaction is potentially reversible
• identified in the past as ‘nuisance dusts’ or ‘inert particulates’
– misleading term which suggests that these materials are harmless – all materials are potentially toxic at sufficiently high doses
• ‘pulmonary overload’ concept
– inert particulates may cause harm by overloading lung tissues
• ‘generic particle’ concept
– inert particulates can contribute collectively to pulmonary overload
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• ACGIH has introduced a TLV occupational exposure limit for PNOC
– ACGIH TLV exposure limits are intended as a guideline (not legally binding)
PNOCs have their own occupational exposure limits
• PNOC definition -- dusts defined as PNOC if they fulfill all 3 criteria:
– insoluble mineral dusts (excludes biological dusts, soluble chemicals) – inhalable dusts that contain <1% crystalline silica and no asbestos – dusts with no other TLV value to control exposure
• TLV - threshold limit value
– maximum allowable air exposure for hazardous substances in workplace air – commonly based on time-weighted average exposure level (TWAEL) of worker
• 40 hours per week for 50 weeks per year over working lifetime (approx 30 years)
• ACGIH TLV values for PNOC (1994)
– 10 mg/m3 for inhalable particulate – 3 mg/m3 for respirable particulate
• ACGIH’s most recent TLV’s are legally binding in Ontario (TWAEL)
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