Classificazione delle broncopneumopatie professionali
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Classificazione delle broncopneumopatie professionali
(Maestrelli et al, in Rugarli Ed, in press)
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BRONCHIOLITE OBLITERANTE
• B. cellulata– infiltrazione di neutrofili (acuta) e cellule
mononucleari (cronica)• B. con polipi infiammatori (BOOP)
– lume occupato da tessuto di granulazione
• B. costrittiva– fibrosi acellulata della parete
Istopatologia
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Bronchiolite cellulata
(V. Poletti, 2000)
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BRONCHIOLITE OBLITERANTE
• B. cellulata– infiltrazione di neutrofili (acuta) e cellule
mononucleari (cronica)• B. con polipi infiammatori (BOOP)
– lume occupato da tessuto di granulazione
• B. costrittiva– fibrosi acellulata della parete
Istopatologia
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(V. Poletti, 2000)
Bronchiolite con polipi infiammatori
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BRONCHIOLITE OBLITERANTE
• B. cellulata– infiltrazione di neutrofili (acuta) e cellule
mononucleari (cronica)• B. con polipi infiammatori (BOOP)
– lume occupato da tessuto di granulazione
• B. costrittiva– fibrosi acellulata della parete
Istopatologia
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(V. Poletti, 2000)
Bronchiolite costrittiva
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BRONCHIOLITE OBLITERANTE• B. cellulata
– ostruzione non reversibile – HRTC: albero fiorito
• B. con polipi infiammatori (BOOP)– s. restrittiva, riduzione transfer CO– HRTC: vetro smerigliato
• B. costrittiva– ostruzione non reversibile – HRTC: oligoemia a mosaico, air trapping
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(V. Poletti, 2000)
Bronchiolite con polipi infiammatori
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BRONCHIOLITE OBLITERANTE• B. cellulata
– ostruzione non reversibile – HRTC: albero fiorito
• B. con polipi infiammatori (BOOP)– s. restrittiva, riduzione transfer CO– HRTC: vetro smerigliato
• B. costrittiva– ostruzione non reversibile – HRTC: oligoemia a mosaico, air trapping
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(V. Poletti, 2000)
Bronchiolite costrittiva (HRTC- inspiratorio)
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(V. Poletti, 2000)
Bronchiolite costrittiva (HRTC- espiratorio)
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BRONCHIOLITE PROFESSIONALEEziologia
• Esposizione acuta– ossidi di azoto– anidride solforosa– fosgene– ammoniaca– cloro
• Esposizione cronica
– Acramin-FWN
– Diacetyl
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(Eur Respir J 1998)
22 cases/257operatives
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BRONCHIOLITE OBLITERANTE PROFESSIONALE
Rapidly progressive, fixed airway obstructive disease in popcorn workers: a new occupational pulmonary illness?
(Parmet et al., J Occup Env Med 2002; 44:216-8)
Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant
(Kreiss et al., N Engl J Med 2002; 347:330-8)
Bronchiolitis obliterans syndrome in popcorn production plan workers
(Akpinar-Elci et al., Eur Respir J 2004; 24: 298-302)
Severe fixed obstructive lung disease in flavoring workers
(Kanwal R,Kullman G et al. Proc Am Thorac Soc 2007;4:in press)
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(Eur Respir J 2004)
9 cases/~450 operatives
- 5 mixing room- 4 microwave packaging lanes
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Livelli di diacetyl e polvere respirabile
Area di lavoro Diacetyl(ppm)
Polvere respirabile(mg/m3)
Uffici e varie 0.04 0.05
Manutenzione 0.56 0.11
Confezione 1.88 0.12
Sala miscele 32.27 0.34
(Kreiss et al., N Engl J Med 2002)
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Relazione tra flussi espiratori ed esposizione a diacetyl
75
80
85
90
95
100
105
1° q. (min) 2° quartile 3° quartile 4° q. (max)
FEV 1
(% te
oric
o)
Quartili di esposizione cumulativa
p per trend = 0.02
(Kreiss et al., N Engl J Med 2002)
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0123456789
Tosse, dispnea,sibili
Espettorato Esordio acuto
(Eur Respir J 2004)
Sintomi respiratoriN
° ca
si
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0123456789
Febbre Mialgie Perditapeso >3Kg
Astenia
(Eur Respir J 2004)
Sintomi sistemiciN
° ca
si
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0123456789
Occhi Naso Cute
(Eur Respir J 2004)
Sintomi irritativi
N°
casi
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(Eur Respir J 2004)
Spirometria (n=9)
• S. ostruttiva n= 5
• S. restrittiva n= 1
• S. mista n= 3
• mosaico n= 8
• air trapping n= 8• >parete bronc. n= 8• bronchiectasie n= 5• fibrosi n= 3
HRTC (n=8)
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(Eur Respir J 2004)
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(Eur Respir J 2004)
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Linee Guida per la Sorveglianza Sanitaria dei lavoratori esposti ad agenti irritanti e tossici
per l’apparato respiratorio
01020304050607080
Asma AAE Pneumocon. BC e altro
%
Distribuzione delle MP respiratorie denunciate all’INAIL- Industria e Agricoltura 2007 -
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Linee Guida per la Sorveglianza Sanitaria dei lavoratori esposti ad agenti irritanti e tossici
per l’apparato respiratorio
Prevalenza di malattie respiratorie nella popolazione adulta
- Bronchite cronica 10% (De Marco, Thorax 2004)
- BPCO (sintomatica) 4-6% (www:goldbpco.it)- BPCO (broncoostruzione) 8.9% (www:goldbpco.it)
- Asma 6-8% (Viegi, Int J Tub Lung Dis 1999)
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Global Initiative for Chronic Obstructive Lung Disease
In collaboration with:
National Heart, Lung, and Blood Institute, NIH
andWorld Health Organization
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http://www.goldcopd.orghttp://www.goldcopd.org
http://www.goldbpco.it http://www.goldbpco.it
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Definition of COPD COPD is a preventable and treatable disease
with some significant extrapulmonary effects that may contribute to the severity in individual patients.
Its pulmonary component is characterized by airflow limitation that is not fully reversible.
The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.
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Burden of COPD: Key Points
• COPD is a leading cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing.
• COPD prevalence, morbidity, and mortality vary across countries and across different groups within countries.
• The burden of COPD is projected to increase in the coming decades due to continued exposure to COPD risk factors and the changing age structure of the world’s population.
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Of the six leading causes of death in the United States, only COPD has been increasing steadily since 1970
Source: Jemal A. et al. JAMA 2005
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Risk Factors for COPD
Host Factors Genes (e.g. alpha1-antitrypsin deficiency)
HyperresponsivenessLung growth
Exposure Tobacco smokeOccupational dusts and chemicalsInfectionsSocioeconomic status
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Risk Factors for COPD
NutritionNutrition
InfectionsInfections
Socio-economic Socio-economic statusstatus
Aging PopulationsAging Populations
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Pathogenesis of COPD
NOXIOUS AGENT(tobacco smoke, pollutants, occupational
agent)
COPD
Genetic factorsRespiratory infectionOther
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BASI MORFOLOGICHE DELLA OSTRUZIONE AL FLUSSO AEREO NELLA BPCO
INFIAMMAZIONE
Bronchiolite ostruttiva Enfisema
RIDUZIONE DEL FLUSSO AEREO
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Manifestazioni fisiopatologiche della BPCO
• Ipersecrezione mucosa e disfunzione ciliare
• Ostruzione al flusso aereo• Iperinflazione polmonare• Anormalità degli scambi gassosi• Ipertensione polmonare• Cuore polmonare
in ordine crescente di gravità
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SYMPTOMScough
sputumdyspnea
EXPOSURE TO RISKFACTORS
tobaccooccupation
indoor/outdoor pollution
SPIROMETRY
Diagnosis of COPD
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Importanza delle cause professionali della BPCO
• BPCO malattia frequente della popolazione
• piccolo aumento prevalenza = grande impatto
• cause professionali: prevenibili
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Cause professionali della BPCO
Bibliografia• American Thoracic Society Statement:
Occupational contribution to the burden of airway disease. Am J Respir Crit Care Med 2003; 167: 787-797.
• Burge PS, Occupational chronic obstructive pulmonary disease. Eur Respir Mon 1999; 11: 242-254.
• Hnizdo et al. Chronic airway disease due to occupational exposure. In: Asthma in the workplace, 3rd ed, 2006: ch 28:683-712.
• http://www.goldcopd.it
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Difficoltà nello studio della BPCO professionale
• multifattoriale• caratteristiche indistinguibili• dose-risposta difficile da quantificare• relazione temporale (lunga latenza)• “healthy workers effect”• studi longitudinali: perdita di lavoratori
dimessi• studi cross-sectional: no declino del FEV1
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Plausibilità biologica della BPCO professionale
Teorica
• fumo = maggior causa di BPCO• non dovuta un singolo componente• simili componenti nell’inquinamento atmosferico• relazione inquinamento atmosferico - BPCO• esposizione lavorativa > inquinamento
atmosferico
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Plausibilità biologica della BPCO professionale
Epidemiologica• 6% di BPCO in non fumatori (USA 1988-94)• occupazioni associate a >RR:
– miniera di carbone, lavoro in galleria, cemento– fornaci, fonderie, cadmio– agricoltura– fibre tessili, endotossine– solventi organici– legno e carta– anidride solforosa, gas nitrosi– polveri, fumi gas/vapori lavoro industriale
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Plausibilità biologica della BPCO professionale
Sperimentale
• agenti capaci di indurre BPCO:– anidride solforosa– polveri minerali– vanadio– endotossine– silice– cadmio– polvere di carbone
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Metodi di studio della BPCO professionale
• Community based vs Industry specific• Dfz BPCO:
– bronchite cronica– funzione respiratoria– dispnea/sibili
• PAR: population attributable riskPAR= N1 (R1-R0)
N1R1+N0R0
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PAR due to occupation for COPD
Community based studies:• Summary = 10-20% of COPD (~30% in non
smokers)• Chronic bronchitis
– dust>gas– equivalent to 10 cig/day
• Excess of FEV1 decline– dust = 7 ml/yr (cigarette smoking 10 ml/yr)
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PAR due to occupation for COPD
Industry specific:• polveri silicotigene (> in fumatori)• polvere di carbone• fibre ceramiche (in fumatori)• isocianati (in non fumatori)• cadmio• polveri vegetali (granaglie, cotone)• endotossine