Respirology & Internal Medicine & Family Medicine
Pulmonary emphysema
Pulmonary emphysema is defined anatomopathologically as permanent and irreversible destruction of the alveolar walls - without significant fibrosis - leading to abnormal and permanent enlargement of the distal airspaces located downstream of the terminal bronchioles. This destruction leads to a loss of gas exchange surface area (normal alveolar surface area: 70-100 m² → reduced to 20-30 m² in advanced forms), reduced pulmonary elasticity and premature expiratory collapse of the small airways (air trapping) → static and dynamic pulmonary hyperinflation → limitation of expiratory flow rates → progressive dyspnoea. Together with chronic bronchitis, emphysema constitutes one of the two main anatomical components of chronic obstructive pulmonary disease (COPD) - although the two entities frequently coexist, emphysema predominates in the so-called «pink puffer» phenotype (lean, dyspneic patient in the foreground, little bronchial hypersecretion, PaO₂ relatively preserved at rest, normal or low PaCO₂). The main and by far predominant cause is active smoking (responsible for 85-90 % of cases) - inhalation of tobacco smoke activates alveolar macrophages and neutrophils → release of proteases (elastase, metalloproteinases - MMP-9, MMP-12) → destruction of elastin and collagen in alveolar walls - a process aggravated by inactivation of endogenous antiproteases (alpha-1 antitrypsin) by free radicals in tobacco smoke. Alpha-1 antitrypsin (AAT) deficiency - a Z mutation (PiZZ) in the SERPINA1 gene - is the most common genetic cause of emphysema (1-2 % of COPD cases) and should be systematically investigated in all young (<45 years), non-smoking emphysematous patients, or those with basal predominance of emphysema on CT scan. In Quebec, COPD affects around 8-10 % of the adult population over 40, and is the 3rd leading cause of death from chronic disease after cardiovascular disease and cancer.
Pathophysiology, anatomical types and clinical presentation
- Anatomical types of emphysema : centrolobular (centro-acinar) emphysema - most frequent - destruction of respiratory bronchioles and proximal alveolar ducts → predominance in the upper lobes → directly linked to smoking; panlobular (pan-acinar) emphysema - uniform destruction of the entire acinus → predominance in the lower lobes → characteristic of AAT deficiency (PiZZ) but also observed in advanced stages of smoking ; paraseptal (subpleural) emphysema - destruction of distal alveoli near interlobular septa and pleura → subpleural bullae → risk of spontaneous pneumothorax (especially in tall, slender young adults); cicatricial (paracicatricial) emphysema - around fibrotic lesions (tubercular sequelae, silicosis)
- Clinical presentation and course : progressive exertional dyspnoea (cardinal symptom - insidious, often trivialized by the patient for years) → rest dyspnoea in advanced stages; progressive limitation of daily activities (mMRC scale: grade 0 to 4); chronic productive cough if associated chronic bronchitis (absent or only slightly marked in pure emphysema); thoracic distension (barrel chest, hypersonority on percussion, diminished vesicular murmurs, prolonged expiration pursed lips); signs of hyperinflation: horizontalized ribs, flattened diaphragms, enlarged retrosternal space on radiography; weight loss, muscle wasting (respiratory cachexia) in advanced stages; cyanosis and digital hippocratism rare in pure emphysema (more frequent in hypercapnic chronic bronchitis)
- Complications : Acute exacerbations of COPD (AEBPD) - acute worsening of dyspnea + increase in secretions + change in their appearance - triggered by viral infections (rhinovirus, influenza - 50-70 %) or bacterial infections (H. influenzae, M. catarrhalis, S. pneumoniae) or by pollution; secondary spontaneous pneumothorax (subpleural bullae rupture - emergency); secondary pulmonary hypertension (PHT) → cor pulmonale → right heart failure (edema, jugular turgor, hepatomegaly); hypoxemic chronic respiratory failure (PaO₂ <60 mmHg at rest → indication for long-term oxygen therapy - LTO); secondary polyglobulia (compensation for chronic hypoxemia)
- Alpha-1 antitrypsin (AAT) deficiency : SERPINA1 gene - hepatic inhibitory protease → normal serum AAT level: 1.0-2.0 g/L; PiZZ genotype → AAT <0.5 g/L → panlobular emphysema predominating at bases + liver disease (cirrhosis - 10-15 % of PiZZ adults) + vasculitis (rarely); age of onset: 30-50 years in PiZZ smokers, 50-60 years in PiZZ non-smokers; screening: serum AAT assay + phenotyping (isoelectrofocalization) or genotyping (PCR alleles S and Z); specific treatment: IV infusion of purified human AAT (Prolastin, Zemaira) - 60 mg/kg/week - slows progression in PiZZ with predicted FEV1 35-60 % (RAPID trial - Chapman 2015 - NEJM)
Diagnosis and treatment
| Appearance / Treatment | Mechanism, technique and procedures | Interpretation, targets and precautions |
|---|---|---|
| Post-bronchodilator spirometry Gold standard COPD/emphysema diagnosis |
Measurement of lung volumes and flows after administration of a short-acting bronchodilator (salbutamol 400 µg); key parameters: FEV1 (forced expiratory volume in 1 second); FVC (forced vital capacity); FEV1/FVC ratio; COPD confirmed if FEV1/FVC <0.70 post-bronchodilator (GOLD 2023 criteria); severity according to predicted FEV1 %: GOLD 1 ≥80 % (mild); GOLD 2 50-79 % (moderate); GOLD 3 30-49 % (severe); GOLD 4 40 % (hyperinflation) + decreased DLCO (diffusion capacity of CO - reflects loss of alveolar surface area - very sensitive for emphysema) | Spirometry is under-utilized in primary care in Quebec - screening recommended in all smokers or ex-smokers ≥40 years with dyspnea or chronic cough (GOLD 2023 + SPLF); fixed FEV1/FVC ratio <0.70 is criticized in elderly subjects (overestimation of COPD - use LLN ratio - Lower Limit of Normal - based on GLI-2012 reference equations) ; partial reversibility to bronchodilator does not exclude COPD or emphysema (unlike pure asthma - complete reversibility); body plethysmography for accurate measurement of static lung volumes (RV, CPT) if spirometry insufficient |
| High-resolution chest CT (HRCT) Emphysema quantification and phenotyping |
Injection-free chest CT scan in millimetric slices (HRCT): direct visualization of areas of alveolar destruction → hypodense patches with no visible wall (centrilobular emphysema: centrilobular distribution predominating at the apexes; panlobular: diffuse destruction of the lower lobes - AAT); lung densitometry score: percentage of voxels 1 cm); evaluation of bronchi (bronchial parietal thickening = chronic bronchitis), air trapping on expiration, pulmonary nodules (lung cancer screening) | Indication for CT: diagnostic confirmation if spirometry equivocal + preoperative workup (volume reduction surgery or transplantation) + lung cancer screening (LDCT - low dose CT - recommended annually for smokers aged 50-80 with ≥20 pack-years - USPSTF 2021 + Quebec program under development) + evaluation of bullae for bullectomy + suspicion of AAT (basal predominance); CT is not systematically recommended for the diagnosis of COPD - spirometry remains the reference tool. |
| Inhaled bronchodilators - BACA, LABA, LAMA Basic pharmacological treatment |
Short-acting bronchodilators (SABA): salbutamol (Ventolin) 100 µg/puff - 1-2 puffs as needed (rapid symptomatic relief - time 5 min - duration 4-6h); long-acting beta-2 bronchodilators (LABA): formoterol (Foradil) 12 µg/capsule 1×/d or salmeterol (Serevent) 50 µg 2×/d - duration 12h; indacaterol (Onbrez) 150-300 µg 1×/d - duration 24h; long-acting anticholinergic bronchodilators (LAMA): tiotropium (Spiriva) 18 µg 1×/d - reduces dynamic hyperinflation, improves exercise tolerance, reduces exacerbations (UPLIFT trial - Tashkin 2008 - NEJM); umeclidinium (Incruse) 62.5 µg 1×/d ; glycopyrronium (Seebri) 50 µg 1×/d; double bronchodilation LABA+LAMA (uméclidinium/vilantérol Anoro; indacaterol/glycopyrronium Ultibro; formoterol/aclidinium Duaklir): superior to monotherapy on symptoms and exacerbations (FLAME trial - Wedzicha 2016 - NEJM) | GOLD 2023 treatment strategy according to ABCD group (symptoms - mMRC/CAT score - + risk of exacerbations): group A (little symptomatic, low risk) → BACA as needed or LABA or LAMA; group B (symptomatic, low risk) → LABA + LAMA from the outset; group E (high risk of exacerbations) → LABA + LAMA ± ICS if blood eosinophils ≥300/µL or if asthma-BPCO overlap; inhaled corticosteroids (ICS): not recommended as monotherapy in COPD - used as triple therapy (LABA + LAMA + CSI) if eosinophils ≥300/µL + frequent exacerbations (IMPACT trial - Lipson 2018 - NEJM - reduction in exacerbations 15 % vs double bronchodilation) |
| Respiratory rehabilitation and smoking cessation The most effective interventions for survival |
Smoking cessation: MOST effective intervention for slowing emphysema progression and reducing mortality (Lung Health Study - Anthonisen 1994 - JAMA - 50 % reduction in annual decline in FEV1); multimodal approach: motivational counseling (5A - Ask, Advise, Assess, Assist, Arrange) + nicotine replacement therapy (NRT - patches, gums, inhalers) + varenicline (Champix - 1 mg × 2/d × 12 weeks - NNT 5-6 - 1st line CPAM 2023) + bupropion (Zyban - 150 mg × 2/d - 2nd line); respiratory rehabilitation (RR): supervised multidisciplinary program (8-12 weeks minimum) - aerobic exercise + muscle strengthening + education + psychosocial + nutritional support → significant improvement in dyspnea (Borg score), exercise tolerance (TM6 - 6-min walk test) and quality of life (St. George's Respiratory Questionnaire). George's Respiratory Questionnaire) - Cochrane McCarthy 2015 - benefit maintained 12-18 months | Respiratory rehabilitation is under-referenced in Quebec despite its level of evidence (A - GOLD 2023) - accessible in university hospital centers and some GMF-Us; RR is reimbursed by RAMQ as part of specific programs; nutritional: correction of malnutrition (target BMI ≥21 kg/m²) + protein supplementation if reduced muscle mass → improves survival; vaccinations: annual influenza + pneumococcus (PCV20 or PPV23 + PCV13 - reduces infectious exacerbations) + COVID-19 + Tdca |
| Long-term oxygen therapy (LTO) and surgical procedures Advanced stages - GOLD 3-4 |
OLD: indicated if PaO₂ ≤55 mmHg at rest (or ≤59 mmHg with polyglobulia or cor pulmonale) measured 2 times at 3-week intervals in stable state → target SaO₂ ≥90 % (PaO₂ 60-65 mmHg) - flow rate 1-3 L/min - minimum duration 15-18h/day (NOCTURNAL oxygen therapy trial + MRC trial - mortality reduction 30-50 % at 5 years if used ≥15h/d) ; nocturnal non-invasive ventilation (NIV) : indicated if severe chronic hypercapnia (PaCO₂ >55 mmHg) + recent hospitalization for hypercapnic exacerbation (HOT-HMV trial - Murphy 2017 - NEJM - reduced rehospitalizations); lung volume reduction surgery (LVRS): resection of the most severe areas of emphysema (upper lobes - heterogeneous emphysema) → improvement in FEV1 + quality of life + survival in selected patients (NETT trial - Fishman 2003 - NEJM); lung transplantation (refractory terminal emphysema - BODE index ≥7) | DLO must be used ≥15-18h/day to be effective (studies have shown no benefit if 96 % (risk of aggravated hypercapnia - hypoxic drive); endobronchial valve (Zephyr, Spiration): minimally invasive alternative to endoscopic CRVP in patients with heterogeneous emphysema + absence of CLP (collateral lung pathways - evaluation by Chartis perfusion scanner) - significant reduction in RV and improvement in FEV1 (LIBERATE trial - Criner 2018 - AJRCCM); roflumilast (Daxas) 500 µg/day po - phosphodiesterase-4 inhibitor - reduces exacerbations in GOLD 3-4 patients with predominant chronic bronchitis (Calverley 2009 - Lancet) |
ℹ️
Visit alpha-1 antitrypsin (AAT) deficiency is the most common genetic cause of emphysema and is chronically under-diagnosed - it is estimated that only 5-10 % of PiZZ individuals in Canada have been diagnosed. Screening is recommended in any patient with COPD or emphysema diagnosed before the age of 45, in non-smokers or light smokers with emphysema, in cases of base-predominant emphysema on CT, and in first-degree relatives of a confirmed case. The initial screening test is the serum AAT assay ( <0.8 g/L suspect - confirm by phenotyping or genotyping). In Quebec, replacement therapy with purified AAT (Prolastin or Zemaira) is available, but access via the RAMQ is subject to strict criteria (confirmed PiZZ + predicted FEV1 25-65 % + non-smoker).
Emergency - Severe acute exacerbation and pneumothorax
Dial 911 or go immediately to the emergency room if an emphysematous patient presents : severe dyspnea at rest or sudden worsening uncontrollable by the usual bronchodilators; ; cyanosis lips or extremities; ; confusion, drowsiness or agitation (signs of acute hypercapnia - CO₂ narcosis); ; sudden unilateral chest pain + sudden dyspnea (secondary spontaneous pneumothorax - vital emergency in advanced emphysema) ; HR >120 bpm + RF >30/min at rest.
The administration of high-concentration oxygen in a chronically hypercapnic COPD patient can worsen CO₂ retention - target SaO₂ 88-92 % in pre-hospital and emergency care (Venturi mask 24-28 %).
Consult at Clinique Omicron
Clinique Omicron's physicians manage patients with emphysema and COPD - diagnostic spirometry, assessment of severity (mMRC score, CAT), prescription of appropriate inhaled bronchodilators, support for smoking cessation, screening for AAT deficiency, vaccination, and referral to respiratory rehabilitation or pulmonology depending on severity. Longitudinal follow-up of stable patients is provided at our points of service in Quebec and via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The contents of this page are provided for information purposes only and do not replace the advice of a qualified healthcare professional. Any worsening of dyspnea in an emphysematous patient requires immediate medical evaluation.
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