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🌱 來自: Huppert’s Notes
Obstructive Lung Diseases🚧 施工中
Obstructive Lung Diseases
• Obstructive = ↑compliance, ↓elastance → problem emptying the lung.
- ↑TLC, ↑RV, problem pushing air out → air trapping
- ↓↓FEV1 ↓FVC = FEV1/FVC ratio <0.7
Chronic obstructive pulmonary disease (COPD)
• Epidemiology: Most common in former smokers (although can affect persons in cities with air pollution, women may develop with less significant smoking history). Typical onset age >40 yr
• Definitions:
- COPD: Persistent airflow limitation resulting from the consequences of chronic inflammation from smoking. Classic subtypes were chronic bronchitis and emphysema, although these are not included in the current definition
• Chronic bronchitis: Clinical diagnosis of chronic productive cough for 3 mo/yr for >2 yr. Normal DLCO.
• Emphysema: Pathologic diagnosis that describes permanent enlargement of the airspaces and destruction of the alveoli, which causes loss of diffusing capacity and reduced elastic recoil. ↓DLCO.
- Centrilobular: Tobacco activates PMNs, inhibits α1-antitrypsin, ↑oxidative stress. Upper lung predominant.
- Panlobular: Alpha-1 antitrypsin deficiency. Lung bases with bilateral basilar bullae and can also have liver disease (PAS+).
• Small airway disease: Third characteristic feature of COPD. Small bronchioles are narrowed and reduced in number. Small airway destruction is a hallmark of advanced COPD.
- Asthma–COPD overlap syndrome (some reversibility with bronchodilators)
• Pathogenesis:
- Airways: Chronic inflammation, increased numbers of goblet cells and mucous glands; airway collapse due to the loss of tethering caused by alveolar wall destruction
- Lung parenchyma: Affects structures distal to the terminal bronchiole
- Pulmonary vasculature: Smooth muscle hypertrophy → chronic hypoxic vasoconstriction of the small pulmonary arteries
• Clinical presentation: Dyspnea, chronic cough, sputum production
• Physical exam:
- Early in disease: Normal or only prolonged expiration or wheezing on forced exhalation
- Increasing severity: Hyperinflation (increased resonance to percussion), decreased breath sounds, wheezes/crackles
- Pearl: Clubbing is NOT typical in COPD; suggests comorbidities such as lung cancer, ILD, or bronchiectasis
• Diagnosis:
- CXR may be normal, as evidence of hyperinflation often not present; CXR is only 50% sensitive for detection of COPD
- PFTs: ↓FEV1, FEV1/FEC <0.70, ↑TLC,↑RV
- Consider testing for alpha-1 antitrypsin deficiency in young patients (<45 yr) or non/minimal smokers. Patients with alpha-1 antitrypsin deficiency may also have liver disease
- Rule out other causes of subacute/chronic dyspnea (e.g., consider BNP, TTE, chest imaging including CT-PE)
• Characterization:
- Characterize symptom burden and risk of exacerbation using the GOLD Group A-D classification system
• Based on exacerbation history (# exacerbations per year and # resulting in hospital admission) and symptom burden (measured by questionnaires such as mMRC, CAT)
• Chronic treatment:
- Three things improve survival: 1) Smoking cessation; 2) Home supplemental oxygen (if PaO2 <55 mmHg, cor pulmonale); 3) Lung volume reduction surgery
- Initial treatment regimen: Here is a general approach, which much be tailored for each patient:
• Start by prescribing a short-acting beta agonist (SABA) or short-acting muscarinic antagonist (SAMA) to be used as needed
• Add a long-acting muscarinic antagonist (LAMA) (e.g., Spiriva)
• Add a long-acting beta agonist (LABA)
• Add an inhaled corticosteroid (ICS)
- Treatment of refractory COPD:
• Consider adjuvant therapies like a PDE4 inhibitor (roflumilast) if inflammation is a significant factor or chronic azithromycin to prevent recurrent exacerbations
• If failing triple therapy (LAMA/LABA/ICS) and eosinophilia is present, consider targeted therapies for eosinophilic lung disease
• For select patients with apical predominant refractory disease, surgery may be an option
• Recommend pulmonary rehabilitation as evidence demonstrates substantial impact on quality of life
• Treatment of acute COPD exacerbation:
- History of prior exacerbations is the best predictor of recurrent exacerbation (ECLIPSE trial, New Engl J Med 2010)
- Cardinal symptoms: Increased dyspnea, sputum quality, sputum purulence
- Etiology: Viral/bacterial infection (70%), inhaler nonadherence, pollution/poor air quality, forest fires, pulmonary embolism, idiopathic
- Management:
• Bronchodilator β2-agonist (albuterol) and anticholinergic (ipratropium)
• Systemic corticosteroids
- Improve FEV1/SpO2, shorten recovery time/length of stay
- PO as effective as IV, benefit may be greatest if peripheral eosinophilia is present
- Prednisone 40 mg PO × 5 days (noninferior for preventing re-exacerbation compared to 14-day course, REDUCE trial, JAMA 2013)
• Supplemental O2 (SpO2 goal 88–92%), avoid hyperoxia
• Ventilatory support
- Indicated for acute hypercapnic respiratory failure
- Benefit demonstrated for non-invasive positive pressure ventilation
- Reassess in 1–2 hours; if not improving, consider intubation
• Antibiotics
- Consider use of antibiotics if 3/3 cardinal symptoms present, 2/3 with one being sputum purulence, or if the patient requires non-invasive mechanical ventilation
- Total antibiotic course typically 5–7 days
- Drug choice based on local antimicrobial resistance. Commonly used: doxycycline, azithromycin
• Prevention:
- Influenza vaccine annually
- Pneumonia vaccines: PCV13 (if not previously given) followed by PPSV23 ≥8 weeks later, then PPSV23 q5yr
• Complications:
- Compensatory polycythemia (Hct >55% men, >47% women)
- Pulmonary hypertension
- Compensatory metabolic alkalosis: Check BMP to assess for elevated HCO3
Asthma
• Pathogenesis: Triad: 1) Airway inflammation, 2) Airway hyper-responsiveness, 3) Reversible airflow obstruction
• Clinical presentation: Shortness of breath, wheezing
• Asthma syndromes: There are many asthma syndromes/variants:
- Allergic asthma: +IgE
- Cough-variant asthma
- Exercise-induced bronchospasm
- Occupational asthma: Farmers, factory workers, and other exposures.
- Aspirin-exacerbated respiratory disease: “Samter’s triad”: Asthma, sinus inflammation with nasal polyps, and sensitivity to aspirin/NSAID. Avoid aspirin/NSAIDS or consider aspirin desensitization.
- Reactive airways dysfunction syndrome: Syndrome of acute airway hyperreactivity in response to an inhaled irritant; NOT to be confused with the sometimes nonspecifically used term “reactive airways” or “airway reactivity” to describe transient wheezing.
- Allergic bronchopulmonary aspergillosis (ABPA): Chronic hypersensitivity in response to colonization with Aspergillus, typically in patients with asthma or cystic fibrosis. Clinical features: Recurrent exacerbation of asthma, peripheral eosinophilia, high IgE titers, +Aspergillus IgG/IgE, radiographic findings (classically central bronchiectasis, upper lobe parenchymal opacities). Tx: Steroids, consider antifungals in some cases.
• Differential diagnosis:
- Virus-induced bronchospasm
- Chronic eosinophilic pneumonia (CEP): Idiopathic disorder with accumulation of eosinophils in the interstitium/alveoli. Median age of onset 30–40 yr. Clinical features: Fever, dyspnea, productive cough, weight loss, wheezes or crackles, peripheral eosinophilia. Classic CXR = bilateral peripheral/pleural-based opacities. Tx: Steroids.
- Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss): Clinical features: Chronic rhinosinusitis, asthma, and pronounced peripheral eosinophilia. +pANCA. Tx: Steroids. If refractory, consider cyclophosphamide and/or other adjuvant therapies
- Vocal cord dysfunction: Consider if the patient is diagnosed with “asthma” but does not improve with treatment or if the patient dramatically improves immediately with intubation. In some cases worsened by stress or can be induced by patient “on command.” Diagnosed by direct laryngoscopy or characteristic flow – volume loop on PFT.
• Common comorbidities: GERD, sinus disease, OSA, obesity. Management of these comorbidities may improve asthma symptoms
• Diagnosis: PFTs; spirometry before and after albuterol administration (increase in FEV1 ≥12% = “reversibility”); bronchoprovocation test (i.e., methacholine, a synthetic choline ester)
• Classification: Asthma severity is characterized by impairment from symptoms and risk of exacerbation requiring oral steroids (Table 2.6)
TABLE 2.6 • Classifications of Asthma: Clinical Features and Recommended Treatments
• Chonic treatment:
- Initial controller therapy is based on classification (Figure 2.12)
FIGURE 2.12: Selecting Initial Controller Treatment in Adults with Asthma. Abbreviations: PFT = pulmonary function test, ICS = inhaled corticosteroid, PRN = pro re nata, a.k.a. as needed; LABA = long-acting beta agonist
- Step-up therapy is based on the principles of Assess, Adjust, and Review Response (GINA Guidelines 2020)
• Assess: Patient’s symptom burden, goals, and inhaler technique
• Adjust: Treat modifiable risk factors, review nonpharmacological strategies, provide education about inhaler use, escalate asthma medications
• Review Response: Symptom burden, exacerbations, side effects, lung function, patient satisfaction
• Treatment of acute asthma exacerbation:
- Clinical features: Dyspnea, wheezing, increased home inhaler use; abnormal peak flow by peak flow meter (in general, <200 L/min consistent with severe obstruction); hypoxia
- Etiology: May be triggered by viruses, allergens, occupational exposures, environmental pollution, aspirin/NSAIDs, exercise, inadequate chronic asthma treatment, or medication non-compliance
- Management:
• Assess severity: HR, RR, O2 saturation, pulsus paradoxus, use of accessory muscles, inability to speak in full sentences
• Evaluate for major risk factors for fatality: 1) Recent history of poorly controlled asthma, 2) Prior history of near-fatal asthma. Minor risk factors = allergies, aspirin-associated asthma
• Provide therapies:
- Supplemental O2 to maintain SpO2 >92%
- Short-acting beta2 agonists (e.g., albuterol nebulizers every 4 hr)
- Ipratropium bromide
- Oral corticosteroids (if used, total duration 5–7 days)
- If severe, consider IV steroids, IV magnesium, and high-dose inhaled corticosteroids
Asthma–COPD overlap syndrome
• Background:
- Asthma/COPD are increasingly recognized as heterogeneous and at times overlapping conditions (Postma et al., New Engl J Med 2015)
• Prototypical versions of each diagnosis differ on several features (e.g., typical age of onset, presence of atopy, smoking history/pack years, reversibility)
- Historical approaches to research have reinforced the asthma and COPD prototypes
• COPD studies excluded nonsmokers or patients with bronchodilator reversibility
• Asthma studies excluded smokers and patients without bronchodilator reversibility
• Treatment: Sporadic trials with various definitions; may be increasingly described in the future, and thus may at some point become an important clinical entity
Bronchiectasis
• Etiology: Irreversible pathologic dilation of the bronchi or bronchioles due to an infectious process occurring in the context of airway obstruction (e.g., tumor, TB, COPD), impaired drainage (e.g., cystic fibrosis, ciliary dysfunction), or abnormality in host antimicrobial defense (e.g., CVID); however, approximately 50% cases ultimately deemed idiopathic
• Clinical presentation: Productive cough (excessive sputum), recurrent pneumonia
• Diagnosis: PFTs with mild moderate obstruction. High resolution chest CT can be used to definitively diagnose
• Treatment: Airway clearance, antibiotic therapy for exacerbations, pulmonary rehabilitation
Cystic fibrosis (CF)
• Etiology: Autosomal recessive mutation in CF transmembrane conductance regulator (CFTR) gene
• Diagnosis: Typically diagnosed in children; occasionally diagnose atypical/delayed presentation in adults. Diagnose by genetic testing (CFTR mutation present) or biochemical testing (sweat test)
• Comorbidities: Diabetes, infertility, osteoporosis, liver disease
• Treatment: Airway clearance, antibiotic therapy, nutritional support including pancreatic enzyme replacement, diabetes management, psychosocial support
• Complications: Bronchiectasis, ABPA, NTM, Burkholderia cepacia infection, sinusitis, male infertility, pancreatitis, intestinal intussusception