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Ähnlich wie Astma i HOBP - sličnosti i razlike (6)
Astma i HOBP - sličnosti i razlike
- 1. ASTMA I HOBP sličnosti i razlikeDejan Žujović Stručni sastanak Gradski zavod za pludne bolesti i tuberkulozu Beograd, 28.03.2013. Gradski zavod za pludne bolesti i tuberkulozu Beograd
- 2. Holandska hipoteza – Orie 1961 Astma i HOBP su različite ekspresije iste bolesti sa preklapanjem kliničkih sindroma: jedna forma može predi u drugu Bronhijalna inflamacija Bronhijalna hiperreaktivnost Genetska predispozicija Faktori sredine Alergija, infekcija, pušenje, zagađenje ASTMA HOBP Bleecker ER. Chest. 2004; 126:93S-95S. Sluiter HJ, et al. Eur Respir J. 1991; 4(4):479-489.
- 3. ATS: Standardi za HOBP 1995 razdvajanje astme i HOBP Hronični bronhitis Emfizem Astma
- 4. Definicija astme Astma je hronična inflamatorna bolest disajnih puteva u kojoj mnoge delije i delijski elementi igraju ulogu. Hronična upala je povezana sa hiperreaktivnošdu disajnih puteva koja dovodi do ponavljanih epizoda otežanog disanja, zviždanja, stezanja u grudima i kašlja, posebno nodu ili u ranim jutarnjim satima. Ove epizode obično su povezane sa rasprostranjenom, ali varijabilnom opstrukcijom koja je često reverzibilna spontano ili uz lečenje. From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2012.
- 5. Simptomi astme i HOBP • Sličnosti - simptomi: ponavljane epizode wheezinga, nedostatka daha, stezanja u grudima i kašlja - obe bolesti imaju pogoršanja koja prate periodi remisije
- 6. Ključne karakteristike astme: da li one prave razliku astme od HOBP? Inflamacija Opstrukcija Reverzibilnost Hiperreaktivnost
- 7. OPSTRUKCIJA DISAJNIH PUTEVA Mesto opstrukcije?
- 8. Sužavanje disajnih puteva u HOBP Normalno HOBP
- 9. Sužavanje disajnih puteva u astmi Normalno Astma
- 10. Mesto opstrukcije prema direktnom merenju – Astma vs. HOBP Pacijenti FEV1% pred Post-BDT R˪ PaO2 Zdravi 88+/-2 3.1+/-0.1 84+/-2 Astma A remisija 90+/-2 2.3+/-0.2 84+/-2 Astma B dugotrajna 55+/-5 9.2+/-1.9 76+/-3 Hronični bronhitis 51+/-5 8.7+/-1.1 71+/-3 Emfizem 39+/-3 5.9+/-0.8 73+/-3 Yanai M, et al. J Appl Physiol. 1992;72(3):1016-23.
- 11. Procenat perifernog otpora prema totalnom otporu direktnim merenjem Pacijenti n Inspirijum Ekspirijum Zdravi 5 24+/-6 33+/-7 Astma Grupa A 10 34+/-5 35+/-6 Grupa B 10 51+/-6* 53+/-5* Hronični bronhitis 7 55+/-3* 56+/-3* Emfizem 8 50+/-4* 53+/-4* Yanai M, et al. J Appl Physiol. 1992;72(3):1016-23. *p ˪ 0.01
- 12. Yanai M, et al. J Appl Physiol. 1992;72(3):1016-23. • Pacijenti sa nedavno pokrenutom astmom imaju vrednosti centralnog i perifernog otpora slično zdravim osobama • Periferni otpor disajnih puteva je značajno povišen kod dugotrajne astme i HOBP • Periferni disajni putevi su osnovno mesto ireverzibilne opstrukcije u astmi i HOBP Mesto opstrukcije disajnih puteva u astmi i HOBP
- 14. Bronhodilatatorni odgovor: HOBP vs. Astma Higgins BG, et al. Eur Resp J. 1991;4:415-20. 0 10 100 1000 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 kumulativne doze (μg) ΔFEV1 n=19 Pacijenti sa astmom ipratropium Pacijenti sa astmom albuterol Pacijenti sa HOBP ipratropium Pacijenti sa HOBP albuterol
- 15. Skoro 2/3 pacijenata sa teškom HOBP (prosečan FEV1 39.3% pred) ima odgovor na bronhodilatatore* Tashkin DP, et al. Eur Respir J. 2008;31:742-50. 65.5% 15 10 5 0 -30 -25 -20 -15 -10 -5 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 UPLIFT Trial (n=5756) ΔFEV1% promena %pacijenata * 15% ili 12% i 200ml porast FEV1
- 16. VARIJABILNOST BRONHODILATATORNOG TESTA 1831 1394 1167 1019 923 96 148 109 39 227 147 111 36 80 37 43 437 238 162 123 39 76 43 33 199 76 48 28 123 51 72 Visita 1: 76% nereverzibilnih Albert P, Agusti A et al. Bronchodilator responsiveness as a phenotypic characteristic of established chronic obstructive pulmonary disease. Thorax. 2012 Aug;67(8):701-8 nereverzibilni reverzibilni Visita 2: 77% nereverzibilnih Visita 3: 77% nereverzibilnih Visita 4: 79% nereverzibilnih
- 17. Heterogenost bronhodilatatornog odgovora u astmi Sharma S, et al. J Allergy Clin Immunol 2008;122:921-8. -20 0 20 40 60 80 600 500 400 300 200 100 0 bronhodilatatorni odgovor (% promene) brojpacijenata CAMP Trial (n=1041) Distribucija bronhodilatatornog odgovora tokom randomizacije
- 18. Heterogenost bronhodilatatornog odgovora u astmi Sharma S, et al. J Allergy Clin Immunol 2008;122:921-8. bez bronhodilatatornog odgovora > 12% i 200ml 0 1 2 3 4 godina brojpacijenata 800 700 600 500 400 300 200 100 0 Bronhodilatatorni odgovor tokom vremena Od 1041 ispitane dece, samo 52 je tokom celog ispitivanja pokazivalo pozitivan bronhodilatatorni odgovor
- 20. Inhalacioni bronhoprovokativni testovi astma, HOBP, zdravi Woolcock AK, et al. Am Rev Respir Dis. 1991; 143:1438-43. doze (μmol) SEVERE MODERATE MILD SLIGHT 0.01 0.1 1.0 10 100 FEV1(%pada) 60 50 40 30 20 10 0 ASTMA HOBP ZDRAVI Metaholin Histamin
- 21. Bronhijalna hiperreaktivnost (BHR) The COPD Lung Health Study • 63% muškaraca i 87% žena pokazuje BHR (≥20% pad FEV1 sa ≤ 25 mg/ml metaholina ukazuje na hiperreaktivnost) • BHR ukazuje na lošu prognozu: povezana je sa bržim propadanjem FEV1 • BHR je povezana sa višim mortalitetom • Prestanak pušenja ima pozitivan efekat na BHR i uzrokuje vede popravljanje FEV1 kod osoba sa BHR Tashkin DP, et al. Am Rev Respir Dis. 1992; 145:301-10. Wise RA, et al. Chest. 2003; 124(2):449-58.
- 22. Definicija HOBP HOBP je bolest koja se može sprečiti i lečiti,a karakteriše je perzistentno ograničenje protoka vazduha u disajnim putevima koje je obično progresivno i udruženo sa povišenim hroničnim inflamatornim odgovorom u disajnim putevima i pludima na štetne čestice i gasove. Egzacerbacije i komorbiditeti doprinose ukupnoj težini kod svakog pojedinačnog pacijenta. From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011.
- 23. Ključne karakteristike HOBP: da li one prave razliku HOBP od astme? Ograničenje protoka vazduha je obično PROGRESIVNO Abnormalni INFLAMATORNI ODGOVOR Značajni VANPLUDNI EFEKTI
- 24. Astma i progresija opstrukcije Peak JK, et al. Eur J Respir Dis. 1987;70:171-79. Zdravi Astma Inflamacija disajnih puteva Remodelovanje Hronična perzistentna opstrukcija disajnih puteva i hiperreaktivnost 20 40 60 80 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 FEV1 (L) Godine života n=278 18 godina pradenja Prosečno propadanje FEV astmatičara 50ml/god zdravih 35 ml/god Efekat varijabilan
- 25. Perzistentna opstrukcija u astmi Procenat pacijenata sa astmom* koji imaju post-BDT FEV1/FVC ˪ 0.7 Kalberg C, et al. Am J Respir Crit Care. 2005. 18-40 godina N=6497 40-60 godina N=3346 > 60 godina N=601 50 45 40 35 30 25 20 15 10 5 0 Pacijenti(%) *Uključeno 10 444 pacijenata iz 38 kliničkih studija astme. Pacijenti imaju dijagnozu astme, bez ostalih značajnih respiratornih oboljenja su (uključujudi HOBP) ˂ 10 paklo/godina pušačke istorije i BDreverzibilnost (≥ 12% post-BD porast nakon albuterola) p ˪ 0.001 za proporciju pacijenata sa fiksiranom opstrukcijom
- 26. INFLAMACIJA
- 27. Inflamacija disajnih puteva HOBP Astma
- 28. Porast eozinofila tokom pogoršanja HOBP Saetta M, et al. Am J Respir Crit Care Med. 1994; 150: 1646-52. 200 150 100 50 0 Stabilna bolest Pogoršanja p ˪ 0.001 EG2(+)delija/mm²
- 29. Porast broja inflamatornih delija i medijatora sa progresijom bolesti 0 20 40 60 80 100 Neutrofili Makrofage Eozinofili CD4 delije CD8 delije B delije Inflamatorne delije GOLD 0 GOLD 1 GOLD 2 i 3 GOLD 4 Disajniputevisa merljivimdelijama(%) Hogg JC, et al. New Engl J Med. 2004; 350(26):2645-53.
- 30. Porast neutrofilne inflamacije u teškoj steroid-zavisnoj astmi 500 1000 2600 2300 1200 ZDRAVI BLAGA/UMERENA ASTMA TEŠKA ASTMA RAZLIKA U BAL DELIJAMA Neutrofili Eozinofili delije/mlBALsadržaja Wenzel SE, et al. Am J Resp Crit Care Med. 1997; 156: 737-43. Statistička razlika između tri grupe za neutrofile i eozinofile je p = 0.032 i p ˂ 0.007 respektivno
- 31. Može li se preporučiti endobronhijalna biopsija u određivanju između astme i HOBP u rutinskoj praksi? • Studija sa 3 patologa (dvostruko-slepa) • 50 uzoraka astme i 50 HOBP • Epitelna dekvamacija (80-98% astma; 61-88% HOBP) i zadebljanje bazalne membrane (71-94% astma; 53-88% HOBP) mogu se povezati sa astmom • Eozinofili snažno usmeravaju patološku dijagnozu u smeru astme, iako je njihova procenjena prevalenca slična (11-37% u astmi i 13-41% u HOBP) Bourdin A, et al. Thorax. 2004; 59(6): 488-93. TrenutnodostupnerutinskeanalizeEBBnisudovoljnodiskriminatorne
- 32. Biomarkeri u razlikovanju astme i HOBP? Fabbri LM, et al. Am J Respir Crit Care Med. 2003; 167: 418-24. Sputum eozinofili Izdahnuti NO
- 33. MOŽEMO LI RAZLIKOVATI ASTMU I HOBP?
- 34. Piras B, Miravitlles M. Multidisciplinary Respiratory Medicine 2012, 7:8 PREVALENCA: 13-20% pacijenata sa HOBP 50% kod starijih od 70 god DIJAGNOZA: 2 major kriterijuma 1 major + 2 minor MAJOR KRITERIJUMI Vrlo pozitivan BDT (> 400 ml i > 15% FEV1) Sputum eozinofilija Prethodna dijagnoza astme MINOR KRITERIJUMI Povedan ukupni serumski IgE Ranija istorija atopije Pozitivan BDT (> 200ml i > 12% FEV1) na najmanje dve posete
- 36. Prirodni tok HOBP Disajnafunkcija Invaliditet → Hronični pušački kašalj Dispneja i intolerancija napora Pogoršanja Hospitalizacije Sistemski efekti Respiratorna insuficijencija Pludna hipertenzija SMRT
- 37. HOBP vs. Astma • SIMPTOMI -Astma je epizodična bolest sa periodima kompletne remisije – obično počinje u detinjstvu -HOBP je progresivno stanje, na početku bolesti pacijent je asimptomatski; kako se bolest pogoršava u srednjim godinama i kasnije, dispneja i pogoršanja su sve češda • SPIROMETRIJA -Kompletna reverzibilnost dijagnostički kriterijum astme
- 39. Difuzijski kapacitet DLco HOBP: DLco SNIŽEN ili normalan Astma: DLco POVIŠEN ili normalan
- 40. Jedna značajna razlika: sistemski efekti HOBP Fabbri LM, et al. Eur Respir J 2008;31:204-12. Poremedaj ishrane Gubitak težine Osteoporoza Metabolički sindrom Dijabetes tip 2 Kardiovaskularni komorbiditet Poremedaj funkcije skeletnih mišida
- 41. Sistemska inflamacija raste sa težinom bolesti Franciosi LG, et al. Pulm Pharmacol Ther. 2006; 19: 189-99. CRP TNF-a Teška HOBP Umerena HOBP Blaga HOBP Zdravi 0 10 20 30 40 50 60 70 0 20 40 60 80 100 Serumski TNF-α (pg/mL)Serumski CRP (mg/L)
- 42. Šta razlikuje astmu od HOBP? I da li je to bitno? DA!
- 43. Terapijski protokoli u stabilnoj HOBP The Cage Study • Vedina blagih pacijenata dobija IKS • Manje od 40% umerenih ili teških pacijenata prima LABA • Samo 51% teških pacijenata koristi dva LABA Bourbeau J, et al. Can Respir J 2008; 15:13-19 n=1090
- 44. Trend mortaliteta u astmi i HOBP Australija 1993-2003 Wilson DH, et al. Med J Aust 2007; 186 (8): 408-411. ASTMA HOBP
- 45. ATS/ERS preporuke 2004 “Pojedini pacijenti sa astmom ne mogu se diferencirati od HOBP postojedim dijagnostičkim testovima. Lečenje ovakvih pacijenata treba da bude identično lečenju astme.”
- 46. “Vredniji je gram iskustva od tovara teorije.” Friedrich Nietzsche
Hinweis der Redaktion
- Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure.Yanai M, Sekizawa K, Ohrui T, Sasaki H, Takishima T.SourceFirst Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.AbstractTo partition the central and peripheral airway resistance in awake humans, a catheter-tipped micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a 3-mm-ID bronchus in 5 normal subjects, 7 patients with chronic bronchitis, 8 patients with emphysema, and 20 patients with bronchial asthma. We simultaneously measured mouth flow, transpulmonary pressure, and intra-airway lateral pressure during quiet tidal breathing. Total pulmonary resistance (RL) was calculated from transpulmonary pressure and mouth flow and central airway resistance (Rc) from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by the subtraction of Rc from RL. The technique permitted identification of the site of airway resistance changes. In normal subjects, RL was 3.2 +/- 0.2 (SE) cmH2O.l-1.s and the ratio of Rp to RL was 0.24 during inspiration. Patients with bronchial asthma without airflow obstruction showed values of Rc and Rp similar to those of normal subjects. Although Rc showed a tendency to increase, only Rp significantly increased in those patients with bronchial asthma with airflow obstruction and patients with chronic bronchitis and emphysema. The ratio of Rp to RL significantly increased in three groups of patients with airflow obstruction (P less than 0.01). These observations suggest that peripheral airways are the predominant site of airflow obstruction, irrespective of the different pathogenesis of chronic airflow obstruction.
- EurRespir J. 1991 Apr;4(4):415-20.Effect of salbutamol and ipratropium bromide on airway calibre and bronchial reactivity in asthma and chronic bronchitis.Higgins BG, Powell RM, Cooper S, Tattersfield AE.SourceRespiratory Medicine Unit, City Hospital, Nottingham, UK.AbstractBronchial reactivity to agonists such as histamine is seen in both chronic bronchitis and asthma, two conditions with different pathological changes in the airways. Salbutamol, when given acutely, reduces bronchial reactivity in patients with asthma, but the mechanism has not been clarified. To determine whether the effect of salbutamol depends on the pathological changes underlying the increased reactivity, we have compared the effect of salbutamol and ipratropium on bronchial reactivity in nine patients with asthma and ten with chronic bronchitis. Each drug was given on separate days in increasing doses (5, 100, 750, 1,000 micrograms) according to a double-blind, randomized design. Changes in forced expiratory volume in one second (FEV1) and specific airways conductance (sGaw) were measured after each dose, and the provocative concentration of histamine causing a 20% fall in the FEV1 (PD20) was determined after the last dose. Salbutamol and ipratropium were equipotent in the asthmatic subjects and caused a similar maximal increase in FEV1 (0.58 and 0.57 l) and sGaw (0.166 and 0.154 s-1.kPa-1). The two drugs also produced similar changes in the patients with chronic bronchitis, although the maximum response to both drugs was smaller (FEV1 0.29 and 0.32 l; sGaw 0.056 and 0.060 s-1.kPa-1; p less than 0.05). Despite differences in bronchodilatation the increase in histamine PD20 following salbutamol was similar in the asthmatic and bronchitic subjects (2.26 and 1.90 doubling doses (DD)) and greater in both groups (p less than 0.05) than the change in PD20 with ipratropium (0.84 and 0.56 DD).(ABSTRACT TRUNCATED AT 250 WORDS)
- AbstractBackground Bronchodilator responsiveness is a potential phenotypic characteristic of chronic obstructive pulmonary disease (COPD). We studied whether change in lung function after a bronchodilator is abnormal in COPD, whether stable responder subgroups can be identified, and whether these subgroups experience different clinical outcomes.Methods 1831 patients with COPD, 285 smoking (SC) and 228 non-smoking (NSC) controls from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) cohort. Spirometric reversibility to 400 μg inhaled salbutamol was assessed on four occasions over 1 year.Results Forced expiratory volume in 1 s (FEV1) increase after salbutamol was similar in SC (mean 0.14 litres (SD 0.15)) and COPD (0.12 litres (0.15)) and was significantly greater than NSC (0.08 litres (0.14)). Reversibility status varied with repeated testing in parallel with the day-to-day variation in pre-bronchodilator FEV1, which was similar in control subjects and patients with COPD. Absolute FEV1 change decreased by Global initiative for chronic Obstructive Lung Disease (GOLD) stage in patients with COPD (GOLD II, mean 0.16 litres (SD 0.17); III, 0.10 litres (0.13); IV, 0.05 litres (0.08) as did chances of being classified as reversible. CT-defined emphysema was weakly related to the absolute change in FEV1 post salbutamol. Consistently reversible patients (n=227) did not differ in mortality, hospitalisation or exacerbation experience from irreversible patients when allowing for differences in baseline FEV1.Limitations Reversibility only assessed with salbutamol and defined by FEV1 criteria. The COPD population was older than the control populations.Conclusions Post-salbutamol FEV1 change is similar in patients with COPD and smoking controls but is influenced by baseline lung function and the presence of emphysema. Bronchodilator reversibility status varies temporally and does not distinguish clinically relevant outcomes, making it an unreliable phenotype.
- BackgroundAmong asthmatic subjects, bronchodilator response (BDR) to inhaled β2-adrenergic agonists is variable, and the significance of a consistent response over time is unknown.ObjectiveWe assessed baseline clinical variables and determined the clinical outcomes associated with a consistently positive BDR over 4 years in children with mild-to-moderate persistent asthma.MethodsIn the 1041 participants in the Childhood Asthma Management Program, subjects with a change in FEV1 of 12% or greater (and 200 mL) after inhaled β2-agonist administration at each of their yearly follow-up visits (consistent BDR) were compared with those who did not have a consistent BDR.ResultsWe identified 52 children with consistent BDRs over the 4-year trial. Multivariable logistic regression modeling demonstrated that lower baseline prebronchodilator FEV1 values (odds ratio, 0.71; P < .0001), higher log10 IgE levels (odds ratio, 1.97; P = .002), and lack of treatment with inhaled corticosteroids (odds ratio, 0.31; P = .009) were associated with a consistent BDR. Individuals who had a consistent BDR had more hospital visits (P = .007), required more prednisone bursts (P = .0007), had increased nocturnal awakenings caused by asthma (P < .0001), and missed more days of school (P = .03) than nonresponders during the 4-year follow-up.ConclusionsWe have identified predictors of consistent BDR and determined that this phenotype is associated with poor clinical outcomes.
- BackgroundAmong asthmatic subjects, bronchodilator response (BDR) to inhaled β2-adrenergic agonists is variable, and the significance of a consistent response over time is unknown.ObjectiveWe assessed baseline clinical variables and determined the clinical outcomes associated with a consistently positive BDR over 4 years in children with mild-to-moderate persistent asthma.MethodsIn the 1041 participants in the Childhood Asthma Management Program, subjects with a change in FEV1 of 12% or greater (and 200 mL) after inhaled β2-agonist administration at each of their yearly follow-up visits (consistent BDR) were compared with those who did not have a consistent BDR.ResultsWe identified 52 children with consistent BDRs over the 4-year trial. Multivariable logistic regression modeling demonstrated that lower baseline prebronchodilator FEV1 values (odds ratio, 0.71; P < .0001), higher log10 IgE levels (odds ratio, 1.97; P = .002), and lack of treatment with inhaled corticosteroids (odds ratio, 0.31; P = .009) were associated with a consistent BDR. Individuals who had a consistent BDR had more hospital visits (P = .007), required more prednisone bursts (P = .0007), had increased nocturnal awakenings caused by asthma (P < .0001), and missed more days of school (P = .03) than nonresponders during the 4-year follow-up.ConclusionsWe have identified predictors of consistent BDR and determined that this phenotype is associated with poor clinical outcomes.
- Eur J Respir Dis. 1987 Mar;70(3):171-9.Rate of decline of lung function in subjects with asthma.Peat JK, Woolcock AJ, Cullen K.AbstractRetrospective and prospective questionnaire and lung function data, collected during seven population health surveys over 18 years in Busselton, Western Australia, have been analysed for 92 subjects with asthma and 186 normal subjects. Subjects who had a minimum of four observations over an 18-year period were selected; the age range at first study was 22-69 years. Individual regression analyses of forced expiratory volume in one second (FEV1), adjusted for height, on age were used in analyses. Subjects with asthma had a greater rate of decline in FEV1 (p less than 0.01) and a lower baseline lung function (p less than 0.001). The mean loss of FEV1 in males of 1.7 m height was 50 ml/year in nonsmokers with asthma compared with 35 ml/year in the normal subjects. The effect of asthma was variable and not all subjects with asthma had steep rates of decline. There were insufficient numbers of smokers with asthma to draw conclusions about an effect of cigarette smoking additional to the effect of asthma. No relationship was found between rate of decline of FEV1 and age or atopic status. In subjects with asthma, bronchial hyperresponsiveness, which was measured at the end of the study, accounted for 9% of the variation in rate of decline of FEV1 and airflow limitation, measured by FEV1 FVC, accounted for 10%. Further studies are needed to determine whether the steep rates of decline found in subjects with asthma are preventable.
- N Engl J Med. 2004 Jun 24;350(26):2645-53.The nature of small-airway obstruction in chronic obstructive pulmonary disease.Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, Paré PD.SourceUniversity of British Columbia, the Centre for Cardiovascular and Pulmonary Research, and St. Paul's Hospital, Vancouver, Canada. jhogg@mrl.ubc.caAbstractBACKGROUND:Chronic obstructive pulmonary disease (COPD) is a major public health problem associated with long-term exposure to toxic gases and particles. We examined the evolution of the pathological effects of airway obstruction in patients with COPD.METHODS:The small airways were assessed in surgically resected lung tissue from 159 patients--39 with stage 0 (at risk), 39 with stage 1, 22 with stage 2, 16 with stage 3, and 43 with stage 4 (very severe) COPD, according to the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD).RESULTS:The progression of COPD was strongly associated with an increase in the volume of tissue in the wall (P<0.001) and the accumulation of inflammatory mucous exudates in the lumen (P<0.001) of the small airways. The percentage of the airways that contained polymorphonuclear neutrophils (P<0.001), macrophages (P<0.001), CD4 cells (P=0.02), CD8 cells (P=0.038), B cells (P<0.001), and lymphoid aggregates containing follicles (P=0.003) and the absolute volume of B cells (P=0.03) and CD8 cells (P=0.02) also increased as COPD progressed.CONCLUSIONS:Progression of COPD is associated with the accumulation of inflammatory mucous exudates in the lumen and infiltration of the wall by innate and adaptive inflammatory immune cells that form lymphoid follicles. These changes are coupled to a repair or remodeling process that thickens the walls of these airways.
- Am J RespirCrit Care Med. 1997 Sep;156(3 Pt 1):737-43.Bronchoscopic evaluation of severe asthma. Persistent inflammation associated with high dose glucocorticoids.Wenzel SE, Szefler SJ, Leung DY, Sloan SI, Rex MD, Martin RJ.SourceDepartment of Medicine, National Jewish Medical and Research Center, Denver, Colorado, USA. wenzels@njc.orgAbstractThe role of inflammation in the pathogenesis of severe asthma chronically treated with high doses of glucocorticoids is poorly understood. Despite this, treatment has been aimed at advancing anti-inflammatory and immunomodulator therapy. This study was designed to evaluate both the presence and type of airway inflammation in patients with severe asthma. A prospective bronchoscopic study evaluated 14 severe, high-dose oral glucocorticoid dependent asthmatics. Bronchoalveolar lavage fluid was analyzed for cytology and inflammatory mediators. Endobronchial and transbronchial biopsies were performed in selected patients for morphometric evaluation of macrophage/monocytes, neutrophils, eosinophils and lymphocytes. These results were compared with lavage and endo- and transbronchial biopsy studies in normal controls and patients with moderate asthma. The concentration of eosinophils in bronchoalveolar lavage fluid was highest in the moderate asthmatics not on glucocorticoids, with very little difference between normal controls and severe asthmatics (significant difference among the groups, p = 0.007). In contrast, the severe asthmatics demonstrated a twofold higher concentration of neutrophils in lavage than either the mild-moderate asthmatics, or the normal controls (p = 0.032 among the groups, p < 0.05 between the severe asthmatics and both controls). Similar results were obtained in the endobronchial and transbronchial biopsy specimens, which consistently showed significantly higher numbers of neutrophils in the severe asthmatics than in the control groups. The eicosanoid mediators, thromboxane and leukotriene B4, were also highest in the severe asthma group (differences among the groups, p = 0.019 and p = 0.023, respectively). These findings suggest that inflammation remains in severe symptomatic asthmatics despite treatment with high dose glucocorticoids which may be due to the severity of disease, glucocorticoid treatment, or other as yet undefined factors.
- Thorax. 2004 Jun;59(6):488-93.Can endobronchial biopsy analysis be recommended to discriminate between asthma and COPD in routine practice?Bourdin A, Serre I, Flamme H, Vic P, Neveu D, Aubas P, Godard P, Chanez P.SourceService des Maladies Respiratoires, Hôpital Arnaud de Villeneuve, CHU de Montpellier, Montpellier, France.AbstractBACKGROUND:International guidelines stress the importance of accurately discriminating between asthma and chronic obstructive pulmonary disease (COPD). Although characteristic pathological features have been described for both conditions, their discriminatory power has never been systematically assessed.METHODS:Endobronchial biopsy (EBB) specimens from patients with a clear clinical diagnosis of asthma and COPD (50 per group) were examined by three pathologists in a double blind manner. They were asked to propose a pathological diagnosis of either asthma or COPD and to analyse qualitatively the most frequent abnormalities reported in the literature.RESULTS:The sensitivity and specificity of EBB ranged from 36% to 48% and from 56% to 79%, respectively. Eosinophils strongly biased the pathological diagnoses in favour of asthma, whereas their estimated prevalence was similar (11-37% in asthma and 13-41% in COPD). Metaplasia (11-39% in COPD, 1-18% in asthma) and epithelial inflammation (28-61% in COPD, 11-38% in asthma) tended to be specific to COPD, whereas epithelial desquamation (80-98% in asthma, 61-88% in COPD) and basement membrane thickening (71-94% in asthma, 53-88% in COPD) tended to be associated with asthma. There was acceptable intra- and inter-observer agreement only for metaplasia and epithelial eosinophils.CONCLUSIONS:Specific histopathological features of asthma and COPD probably exist, but current routine analysis procedures to assess EBB specimens are not sufficiently discriminatory. This might be rectified by improving pathological definitions.
- Am J RespirCrit Care Med. 2003 Feb 1;167(3):418-24. Epub 2002 Nov 8.Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease.Fabbri LM, Romagnoli M, Corbetta L, Casoni G, Busljetic K, Turato G, Ligabue G, Ciaccia A, Saetta M, Papi A.SourceResearch Center on Asthma and COPD, University of Ferrara, Italy. fabbri.leonardo@unimo.itAbstractTo determine whether patients with fixed airflow obstruction have distinct pathologic and functional characteristics depending on a history of either asthma or chronic obstructive pulmonary disease (COPD), we characterized 46 consecutive outpatients presenting with fixed airflow obstruction by clinical history, pulmonary function tests, exhaled nitric oxide, sputum analysis, bronchoalveolar lavage, bronchial biopsy, and high-resolution computed tomography chest scans. Subjects with a history of COPD (n = 27) and subjects with a history of asthma (n = 19) had a similar degree of fixed airflow obstruction (FEV1: 56 +/- 2 versus 56 +/- 3% predicted) and airway hyperresponsiveness (PC20FEV1: 2.81 [3.1] versus 1.17 [3.3]). Subjects with a history of asthma had significantly more eosinophils in peripheral blood, sputum, bronchoalveolar lavage, and airway mucosa; fewer neutrophils in sputum and bronchoalveolar lavage fluid; a higher CD4+/CD8+ ratio of T cells infiltrating the airway mucosa; and a thicker reticular layer of the epithelial basement membrane. They also had significantly lower residual volume, higher diffusing capacity, higher exhaled nitric oxide, lower high-resolution computed tomography scan emphysema score, and greater reversibility to bronchodilator and steroids. In conclusion, despite similar fixed airflow obstruction, subjects with a history of asthma have distinct characteristics compared with subjects with a history of COPD and should be properly identified and treated.
- AbstractBACKGROUND:The information on usual care for patients with chronic obstructive pulmonary disease (COPD) in primary care is limited in Canada.OBJECTIVE:To evaluate primary care practice in patients with COPD in Quebec and Ontario compared with recommended care.METHODS:The COPD Care Gap Evaluation (CAGE) was a prospective, cross-sectional study. Physicians’ self-reported data of enrolled COPD patients were compared with the recommended care for the level of disease severity (using the Canadian Thoracic Society classification by symptoms) and stability, derived from Canadian Thoracic Society COPD guidelines. Pharmacological treatment, spirometric confirmation of diagnosis and nonpharmacological management, including smoking cessation counselling, influenza immunization and referral for pulmonary rehabilitation, were assessed.RESULTS:Participating physicians (n=161; 44 in Quebec, 117 in Ontario) recruited 1090 patients (320 in Quebec, 770 in Ontario). The mean (± SD) age of the patients was 69.9±10.4 years; 60% were male and 40% were currently smoking. Pharmacological treatment that matched guideline recommendations was identified in 34% of patients. Discrepancies between reported and recommended treatment stemmed from nonprescription of long-acting bronchodilators (LABDs) for patients with moderate (27%) and severe (21%) COPD, nonprescription of two long-acting beta agonists (a beta2-agonist and an anticholinergic) for patients with severe COPD (51%), and prescription of inhaled corticosteroids (63%) and LABDs (47%) for patients with mild COPD for which the treatment is not recommended. Spirometric confirmation of diagnosis, as recommended by the guidelines, was reported in 56% of patients. For non-pharmacological management, smoking cessation counselling (95%) and influenza immunization (80%) were near optimal. Referral for pulmonary rehabilitation (9%) was not common. Differences between provinces were seen mainly in the prescription of short-acting bronchodilators (89% in Quebec, 76% in Ontario) and LABDs (60% in Quebec, 80% in Ontario).CONCLUSIONS:Substantial gaps between recommended and current care exist in the management of COPD patients in primary care practice. Undertreatment of patients with severe COPD has potential clinical implications, including loss of autonomy and hospitalization.