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Univ. Prof. Dr. Daiana Stolz MD

8. March 2023

New Lancet Commission’s recommendations on COPD – a proactive approach to managing COPD no one expected?1

Webinar of the 15 december 2022, 17.30–18.30

Keywords: COPD, diagnostic algorithm, classification, Lancet Commission, GOLD Guidelines

Univ. Prof. Dr. Daiana Stolz MD MPH FERS FCCP
Clinic of Respiratory Medicine,
University Hospital Freiburg, Germany
and Clinic of Respiratory Medicine
and Pulmonary Cell Research,
University Hospital of Basel, Switzerland

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Take Home Messages
  • COPD (chronic obstructive pulmonary disease) is considered a pandemic, global health crisis, being the 3rd leading cause of death worldwide in 2019 with an increasing incidence.2
  • A new classification of COPD based on risk factors was suggested, dividing patients into five types (Genetics, Early-life events, Infection, Smoking, Environmental exposure). Pathophysiological mechanisms related to each of these exposures could translate into distinct diagnostic, prognostic, and therapeutic considerations.1 As an example, a biomarker-guided approach («precision therapy») to therapy results in much lower NNT than the overall approach.3
  • Previously COPD could only be diagnosed when spirometry obstruction was present. However, this is very insensitive for early diagnosis and often shows poor association with the severity of symptoms.
  • The Lancet Commission suggests a new diagnostic algorithm with other diagnostic tests, such as imaging with CT or MRI, that enables an earlier recognition and treatment of COPD.1
  • A new more objective definition of COPD exacerbations was suggested. In addition to an increase in classic symptoms (cough, dyspnoea, or sputum production) at least one other factor such as an increase in airflow limitation or ventilation heterogeneity, an increase in airway or systemic inflammation or evidence of bacterial/viral infection should be present.1
  • In addition, the severity of COPD exacerbations should not be judged in terms of the type of treatment or the setting where treatment is provided, but should be ranked according to their severity from one to five based on objective clinical, biological, and physiological criteria.1
  • The new GOLD 2023 Guidelines combine groups C and D into the new group E, emphasizing the importance of exacerbations for the management of COPD1. The recommended initial pharmacological treatment for group E patients is dual bronchodilation with LABA/LAMA unless eosinophils are elevated, indicating a beneficial use of inhaled corticosteroids (ICS) in these patients.
  • When ICS use is indicated, the initial use of FDC-triple-therapy (fixed-dose-combination) ICS/LABA/LAMA (e. g. Trixeo®) is recommended over dual therapy (ICS/LABA) due to its superiority in the reduction of exacerbations.4, 5, 6, 8
  • Noteworthy: only FDC-triple-therapies have demonstrated a significant reduction in all-cause mortality (ETHOS5 [HR = 0.51] and IMPACT6 [HR = 0.72]) compared to dual bronchodilation (LABA/LAMA).4, 5, 6
  • In cases where pharmacological treatment is no longer effective, it is important to consider the option of surgical and minimally invasive surgical treatment. For example, if the disease fulfils certain criteria (e. g. hyperinflation, no collateral ventilation) patients can benefit from bronchoscopic lung volume reduction.

References

  1. Stolz, Daiana et al. Towards the elimination of chronic obstructive pulmonary disease: a Lancet Commission. Lancet (London, England) vol. 400,10356 (2022): 921–972. doi: 10.1016/S0140-6736(22)01273-9.
  2. Ma, Jiemin et al. Temporal Trends in Mortality in the United States, 1969–2013. JAMA vol. 314,16 (2015): 1731–9. doi: 10.1001/jama.2015.12319.
  3. Leung, Janice M, and Don D Sin. Inhaled corticosteroids in COPD: the final verdict is … The European respiratory journal vol. 52,6 1801940. 13 Dec. 2018, doi:10.1183/13993003.01940–2018.
  4. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of COPD 2023 report. Accessed November 17, 2022. https://goldcopd.org/2023-gold-report-2/.
  5. Rabe KF, Martinez FJ, Ferguson GT, Wang C, Singh D, Wedzicha JA, Trivedi R, St Rose E, Ballal S, McLaren J, Darken P, Aurivillius M, Reisner C, Dorinsky P; ETHOS Investigators. Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD. N Engl J Med. 2020 Jul 2; 383 (1): 35–48.
  6. Lipson DA, Crim C, Criner GJ, Day NC, Dransfield MT, Halpin DMG, Han MK, Jones CE, Kilbride S, Lange P, Lomas DA, Lettis S, Manchester P, Martin N, Midwinter D, Morris A, Pascoe SJ, Singh D, Wise RA, Martinez FJ. Reduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2020 Jun 15; 201 (12): 1508–1516.
  7. Bafadhel M, McKenna S, Terry S, Mistry V, Pancholi M, Venge P, Lomas DA, Barer MR, Johnston SL, Pavord ID, Brightling CE. Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial. Am J Respir Crit Care Med. 2012 Jul 1; 186 (1): 48–55.
  8. Ferguson GT, Rabe KF, Martinez FJ, Fabbri LM, Wang C, Ichinose M, Bourne E, Ballal S, Darken P, DeAngelis K, Aurivillius M, Dorinsky P, Reisner C. Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial. Lancet Respir Med. 2018 Oct; 6 (10): 747–758.

Product information TRIXEO AEROSPHERE®
Z: Wirkstoffe: Budesonid, Formoterolfumarat-Dihydrat, Glycopyrronium als Glycopyrroniumbromid, Hilfsstoffe: Norfluran (HFA-134a), 1,2-Distearoyl-sn-glycero-3-phosphocholin (DSPC), wasserfreies Kalziumchlorid; Druckgasinhalation, Suspension. Jeder Sprühstoss (über das Mundstück abgegebene Dosis) enthält 5 µg Formoterolfumarat-Dihydrat, 9 µg Glycopyrroniumbromid (entsprechend 7,2 µg Glycopyrronium) und 160 µg Budesonid. Dies entspricht einer gemessenen Menge von 170 µg Budesonid, 9,6 µg Glycopyrroniumbromid (entsprechend 7,7 µg Glycopyrronium) und 5,3 µg Formoterolfumarat-Dihydrat (entsprechend 5,1 µg Formoterolfumarat); Liste B. I: Erhaltungstherapie bei erwachsenen Patienten mit moderater bis schwerer chronisch obstruktiver Lungenerkrankung (COPD) D: Die empfohlene und maximale Dosis beträgt 2 Sprühstosse 2-mal täglich (2 Sprühstosse am Morgen und 2 Sprühstosse am Abend); Zur Inhalation. KI: Bekannte Überempfindlichkeit gegenüber den Wirkstoffen oder einem der Hilfsstoffe. V: Nicht zur Akuttherapie; Nach der Anwendung von Formoterol/Glycopyrronium/Budesonid kann es u. a. zu einem paradoxen Bronchospasmus, zu einer Verschlechterung der Erkrankung, zu kardiovaskulären Wirkungen, wie z. B. kardialen Arrhythmien, elektrokardiographischen Veränderungen kommen. Vorsicht ist u. a. geboten bei Verlängerung des QTc-Intervalls (QTc > 450 Millisekunden bei Männern bzw. > 470 Millisekunden bei Frauen), einer Narkose mit halogenierten Anästhetika, Schilddrüsenfunktionsstörungen, Diabetes mellitus, Phäochromozytom oder unbehandelter Hypokaliämie. Ferner sind mögliche durch die Wirkstoffe verursachte systemische Nebenwirkungen von Kortikosteroiden, Elektrolytverschiebungen durch Therapie mit Beta-2 Adrenozeptoragonisten und anticholinerge Effekte zu beachten. Patienten mit schwerer Nierenfunktions- und/oder Leberfunktionseinschränkung sollten nur dann mit diesem Arzneimittel behandelt werden, wenn der zu erwartende Nutzen das mögliche Risiko überwiegt. IA: mit starken CYP3A4 Inhibitoren (z. B. Itraconazol, Ketoconazol, HIV Proteasehemmern und Arzneimitteln, die Cobicistat enthalten, Cimetidin); mit anderen Arzneimitteln, die Anticholinergika und/oder langwirksamen Beta2 Adrenozeptoragonisten enthalten; Xanthin Derivate, Steroide und nichtkaliumsparende Diuretika, Betablocker, Chinidin, Disopyramid, Procainamid, Antihistaminika, Monoaminooxidase-Inhibitoren, Grapefruitsaft, trizyklische Antidepressiva, Phenothiazine, Narkose mit halogenierten Kohlenwasserstoffen. L Dopa, L Thyroxin, Oxytocin und Alkohol können die kardiale Toleranz von Beta 2 Sympathomimetika beeinträchtigen. Schwangerschaft, Stillzeit. UAW: häufig: Oropharyngeale Candida-Infektion, Pneumonie, Hyperglykämie, Angstzustände, Schlafstörungen, Kopfschmerzen, Palpitationen, Dysphonie, Husten, Übelkeit, Muskelkrämpfe, Harnwegsinfektionen. Gelegentlich, selten, sehr selten: siehe www.swissmedicinfo.ch. Fachpersonen können die genannten Referenzen bei AstraZeneca AG anfordern. Stand der Information: Januar 2022.

Weitere Informationen: www.swissmedicinfo.ch oder AstraZeneca AG, Neuhofstrasse 34, 6340 Baar. www.astrazeneca.ch

This webinar was supported by AstraZeneca AG and PulmonX International Sàrl.

CH-7248_02/2023
EUR-EN-1786-v1

 

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