Chronic Obstructive Pulmonary Disease Xử trí

Evaluation

Clinical Decision

COPD exacerbation is an event characterized by increased dyspnea and/or cough and sputum that worsens in <14 days with or without tachypnea and/or tachycardia. It is associated with increased local and systemic inflammation. Viral and bacterial respiratory tract infections are the common causes in which 50% of exacerbations are bacterial in etiology. Other causes include air pollution, interruption of maintenance medications, and other comorbidities (eg gastroesophageal reflux disease [GERD]). 

The signs and symptoms of COPD exacerbation include the following: 

• Increased breathlessness, wheezing, and chest tightness
• Increased cough and sputum, change in the color and/or tenacity of the sputum
• Fever, malaise, fatigue, depression, confusion, sleep disturbances, decreased exercise tolerance
• It can be difficult to differentiate from COVID-19 infection which can present with cough and breathlessness but is accompanied by fever, diarrhea, nausea, vomiting, fatigue, confusion, muscle pains, anosmia, dysgeusia, and headache

Assessment of Severity

The severity of COPD is classified based on the patient’s symptoms, spirometry results, presence of complications, and future risk of exacerbations.

The below classification is based on the post-bronchodilator FEV₁ in patients with an FEV₁/FVC ratio of <0.7:

• GOLD 1 (Mild COPD): FEV₁ ≥80% predicted
• GOLD 2 (Moderate COPD): 50% ≤ FEV₁ <80% predicted
• GOLD 3 (Severe COPD): 30% ≤ FEV₁ <50% predicted
• GOLD 4 (Very severe COPD): FEV₁ <30% predicted

The use of a fixed ratio may lead to underdiagnosis in patients <45 years, especially of mild disease and overdiagnosis in patients >50 years.

*Reference: Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report.

Principles of therapy

The goals of pharmacotherapy are prevention and control of symptoms, reduction of the frequency and severity of exacerbations, improvement of health status, improvement of exercise tolerance, prevention of disease progression, and reduction of mortality.

Drug therapy for COPD is determined by individualized assessment of symptoms and exacerbation risk. Based on studies, the existing pharmacotherapy for COPD does not modify the long-term decline in lung function. However, limited evidence suggests that regular treatment with long-acting beta₂-agonists, inhaled corticosteroids (ICS), and its combination can decrease the rate of decline in lung function. 

Pharmacological therapy

Initial Treatment

The following table summarizes initial treatment recommendations by patient category of COPD:

*Reference: Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2024 report.
¹May be considered for patients who have blood eosinophilia ≥300 cells/μL; although, it may increase the risk for pneumonia.

Follow-up Treatment

Follow-up treatment should be based on the predominant symptom, either for dyspnea or persistent exacerbations, irrespective of the patient’s GOLD grouping. Inhaler technique and treatment adherence should be investigated in every follow-up.

Patients may be considered for an additional long-acting bronchodilator if breathlessness or exercise limitation is still present despite inhaled bronchodilator monotherapy.

Dual combination therapy with two long-acting inhaled should be considered in patients previously given short-acting bronchodilators or long-acting inhaled bronchodilator monotherapy who show disease progression. Triple combination therapy should be offered to patients with disease progression despite treatment with a dual bronchodilator (long-acting anticholinergic plus long-acting beta₂-agonist) therapy.

Roflumilast or Azithromycin may be given to patients suffering from persistent exacerbations previously given a bronchodilator combination therapy and with an eosinophil count of <100 cells/µL. Roflumilast should be considered in patients with an FEV₁ of <50% predicted and chronic bronchitis. Azithromycin may be added for patients who are ex-smokers.

Bronchodilators

Classes include anticholinergics, beta₂-agonists, and methylxanthines. All bronchodilators increase the exercise capacity of patients.

Inhaled bronchodilators are recommended for all symptomatic patients with stable COPD with FEV₁ of <60%. They may also be used for symptomatic stable COPD patients with predicted FEV₁ of 60-80%. Inhaled therapy is preferred to oral, because of better efficacy, faster onset, and decreased likelihood of adverse effects.

Short-acting bronchodilators are given on a “when required” basis for immediate relief of symptoms and long-acting bronchodilators are administered on a regular basis to prevent or reduce symptoms

Regular treatment with long-acting bronchodilators is more effective and convenient but can be more expensive. When possible, therapy should be via the inhaled route but if cost is a barrier, then oral bronchodilators (beta₂-agonists) can be considered. Inhaled bronchodilators are preferred to Theophylline because of the latter’s low bronchodilating effect and a high potential for toxicity.

The choice of drugs will depend on the patient’s response and preference, together with the drug’s side effects and cost.

Anticholinergics

Example drugs: Long-acting: Aclidinium, Glycopyrronium, Tiotropium, Umeclidinium; Short-acting: Ipratropium, Oxitropium

Long-acting inhaled anticholinergics work by blocking the effects of acetylcholine on M2 and M3 (short-acting), and M1 and M3 (long-acting) receptors. Long-acting inhaled anticholinergics are recommended for symptomatic patients with FEV₁ of <60% predicted. Short-acting anticholinergics generally have a longer duration of bronchodilatation than short-acting beta₂-agonists.

Based on a large, long-term, randomized, controlled study in patients with moderate to very severe COPD, Tiotropium with concurrent respiratory medication other than another inhaled anticholinergic agent, resulted in positive effects on quality of life, reduced risk of exacerbations and exacerbation-related hospitalizations, and reduced respiratory morbidity including respiratory failure and cardiac morbidity.

Based on short-term, clinical studies in patients with moderate to severe COPD, a combination of short-acting anticholinergic and short-acting beta₂-agonist may provide superior bronchodilatation than either medication alone. Aclidinium and Glycopyrronium have effects on lung function and breathlessness comparable to that of Tiotropium, but further studies are needed.

Anticholinergics have been shown to be very safe in a wide range of doses.

Beta₂-agonists

Example drugs: Long-acting: Arformoterol, Formoterol, Indacaterol, Olodaterol, Salmeterol, Tulobuterol, Vilanterol (given as combination therapy); Short-acting: Fenoterol, Levalbuterol, Salbutamol (Albuterol), Terbutaline  

Beta₂-agonists relax the airway smooth muscle by stimulating beta₂-adrenergic receptors. Long-acting inhaled beta₂-agonists are recommended for symptomatic patients with FEV₁ of <60% predicted.

Salmeterol and Formoterol significantly improve FEV₁, lung function, dyspnea, quality of life, and exacerbation rate. Vilanterol, in combination with Umeclidinium or Fluticasone, showed improved lung function and a slower decline in FEV₁.

Based on several clinical trials, the combination of long-acting beta₂-agonists (eg Salmeterol) and ICS (eg Fluticasone) may reduce COPD exacerbation and may improve lung function and quality of life better than when each drug is used alone.

Inhaled beta₂-agonists have a faster onset of action and fewer side effects than oral preparations.

Methylxanthines

Example drugs: Aminophylline, Theophylline

Methylxanthines may act as a nonselective inhibitor of phosphodiesterase but have also been observed to exert a range of non-bronchodilator actions.

Although they have a modest effect in COPD, inhaled bronchodilators are preferred to Theophylline, owing to the latter’s poor bronchodilating property and potential toxicity. The combination of a beta₂-agonist, an anticholinergic, and Theophylline may produce additional improvements in health status and lung function.

All studies that have shown the efficacy of Theophylline in COPD made use of slow-release preparations.

Combination Bronchodilator Therapy

Available as a single inhaler are Fenoterol/Ipratropium, Salbutamol/Ipratropium, Formoterol/Aclidinium, Formoterol/Glycopyrronium, Indacaterol/Glycopyrronium, Vilanterol/Umeclidinium, and Olodaterol/Tiotropium.  

Bronchodilator-corticosteroid combinations (eg Formoterol/Beclometasone, Formoterol/Budesonide, Formoterol/Mometasone, Salmeterol/Fluticasone propionate, Vilanterol/Fluticasone furoate, Fluticasone/Umeclidinium/Vilanterol, Beclometasone/Formoterol/Glycopyrronium, Budesonide/Formoterol/Glycopyrrolate) are also available.

Combination therapy with inhaled long-acting anticholinergics, long-acting beta₂-agonists, or corticosteroids is recommended for symptomatic patients with stable COPD and FEV₁ of <60% predicted. Combining drugs with different mechanisms of action may increase bronchodilatation with fewer side effects compared to simply increasing the dose of a bronchodilator.

Compared to monotherapy, combination treatment of short-acting beta₂-agonist and short-acting anticholinergics improves FEV₁ and symptoms. Compared to monotherapy, combination treatment of long-acting beta₂-agonist and long-acting anticholinergics increases FEV₁, decreases symptoms, and reduces exacerbation.

Corticosteroids

Example drugs: Inhaled: Beclomethasone, Budesonide, Fluticasone, Mometasone; Systemic: Prednisolone, Methylprednisolone

Regular treatment with ICS alone does not change the long-term decline of FEV₁. Regular treatment with ICS is appropriate in patients with FEV₁ of <50% predicted or ≥2 exacerbations per year and repeated exacerbations (eg 3 exacerbations in the last 3 years). Corticosteroids may reduce airway hyper-reactivity in these patients and decrease the symptoms of COPD including exacerbations.

ICS in combination with 1 or 2 long-acting bronchodilators is recommended in patients with a history of hospitalizations for COPD exacerbations despite appropriate maintenance therapy with a long-acting bronchodilator. The combination is also recommended in patients with ≥2 moderate COPD exacerbations per year despite appropriate maintenance therapy with a long-acting bronchodilator, patients with a history of or concomitant asthma, or patients with a blood eosinophil count of >300 cells/microliter.

In patients with more advanced COPD and repeated exacerbation, treatment with ICS can be beneficial.

The dose-response relationships and long-term safety of ICS in COPD are not known. On a 3-year period, treatment in COPD patients with a high prevalence of osteoporosis, therapy with high-dose Fluticasone alone or in combination with Salmeterol was not associated with decreased bone mineral density compared with placebo. Previous long-term trials investigating bone mineral density in COPD patients produced conflicting results.

The use of combination therapy with ICS and long-acting beta₂-agonist is more effective in reducing exacerbations and improving pulmonary function than either medication alone. In patients with FEV₁ of <60%, treatment with long-acting beta₂-agonist, ICS and its combination have been shown to reduce the rate of decline of pulmonary function. The addition of the combination to an anticholinergic (eg Tiotropium) appears to provide additional benefits.

Triple inhaled therapy (long-acting anticholinergic plus long-acting beta₂-agonist plus ICS) has been shown to improve lung function, symptoms, and health status, and reduce exacerbations compared to combination therapy of ICS and long-acting beta₂-agonist, long-acting beta₂-agonist and long-acting anticholinergic, or monotherapy with a long-acting anticholinergic.

Long-term monotherapy with ICS is not recommended. Long-term use of oral corticosteroids is likewise not recommended. Short-course trials of oral corticosteroids may not reliably predict which patients will respond to ICS.

Phosphodiesterase-4 Inhibitor

Example drug: Roflumilast  

Roflumilast, a phosphodiesterase-4 inhibitor, reduces inflammation through the inhibition of the breakdown of intracellular cyclic adenosine monophosphate (cAMP).  It has no direct bronchodilator effects but has been shown to improve FEV₁ in patients treated with Tiotropium or Salmeterol.

Roflumilast has been shown to reduce exacerbations in patients with severe to very severe COPD (FEV₁ <50% predicted) with chronic bronchitis treated with oral corticosteroids. The same effect on exacerbation reduction has been noted when added to long-acting bronchodilators.

Roflumilast cannot be administered with Theophylline. It has more side effects compared to inhaled medications.

Other Pharmacologic Agents

Alpha-1 Antitrypsin Augmentation Therapy (AAATD)

AAATD may help halt the development and progression of pulmonary disease. Studies demonstrated a reduction in spirometric progression with AATD in patients with FEV₁ of 35-49% predicted. It is especially recommended for nonsmoking patients or those who stopped smoking with FEV₁ of 35-60% predicted. Further studies are needed to prove the efficacy versus cost of this treatment.

Antibiotics

Antibiotics are not recommended except for the treatment of infectious bacterial exacerbations. The regular use of some antibiotics (eg Azithromycin, Erythromycin) may reduce exacerbation rates in patients with COPD patients who are prone to exacerbations. Treatment with macrolides (eg Azithromycin) may be considered for previous smokers with moderate to severe exacerbations despite inhaled bronchodilator therapy.

Cough and Cold Preparations

Example drugs: Ambroxol, Carbocysteine, Erdosteine, N-acetylcysteine  

Antitussives are not recommended because cough has a protective effect in COPD.

Expectorants and mucolytics were seen to have benefits in a few patients with viscous mucous, but overall benefits seem to be very small. They may be considered in patients with chronic cough productive of sputum and therapy may be continued if there is a decrease in the frequency of cough and sputum production.

Regular treatment with Carbocysteine or N-acetylcysteine may help reduce exacerbations in COPD patients without ICS treatment.

Vaccines

Influenza Vaccine

Influenza vaccines may decrease morbidity and mortality rates due to influenza. It should be given yearly, 1-2 months prior to the anticipated peak influenza season, because of new antigens and waning immunity from the previous year. It is associated with a reduced risk of all-cause mortality.

Pneumococcal Vaccines

Example vaccines: 13-valent pneumococcal conjugate vaccine (PCV13), 15-valent pneumococcal conjugate vaccine (PCV15), 20-valent pneumococcal conjugate vaccine (PCV20), and 23-valent pneumococcal polysaccharide vaccine (PPSV23)

Pneumococcal vaccine is recommended in COPD patients ≥65 years old and in younger patients with significant comorbidities (eg cardiac disease, chronic pulmonary disease).

PPSV23 reduces the occurrence of community-acquired pneumonia (CAP) in patients <65 years old with FEV₁ of <40% predicted or comorbidities.

Studies showed that PCV13 exhibited significant efficacy for both CAP and vaccine-type invasive pneumococcal disease in adults ≥65 years old with efficacy lasting for at least 4 years. It possesses comparable or even greater efficacy when compared to the immunogenicity of PPSV23.

Pneumococcal vaccines are generally given only once, but revaccination may be considered in 5-10 years.

COVID-19 Vaccines

COVID-19 vaccines are highly effective against SARS-CoV-2 infection requiring hospitalization. Patients with COPD should be vaccinated in line with the national recommendations for COVID-19 vaccination.

Inhalation Devices

Inhalational devices are effective for drug delivery and training in inhaler technique should be emphasized and re-checked as necessary. The choice of device depends on price, availability, the prescribing doctor, and the skills and ability of the patient. Assessment of the inhaler technique should be done prior to modifying the current therapy.

COPD patients may have poorer coordination and experience more difficulty with metered dose inhaler (MDI) use. The use of spacers with the MDI may be advised for patients who find it hard to master the MDI inhaler technique.

A dry powder inhaler (DPI) is a type of inhaler that is breath-activated and may therefore require less hand-and-mouth coordination. It may be more convenient and may provide improved deposition of the drug.

Nebulizers are not recommended for routine use because of the greater cost of treatment.

Nonpharmacological

Oxygen Therapy and Non-invasive Mechanical Ventilation (NIV)

Oxygen (O₂) Therapy

Long-term administration of O₂ (>15 hours/day) increases survival in patients with chronic respiratory failure. O₂ therapy may also benefit hemodynamics, hematologic characteristics, exercise capacity, lung mechanics, and mental state. 

O₂ therapy is given to patients with stage IV (very severe) COPD with the following: 

• PaO₂ of ≤55 mmHg (7.3 kPa) or oxygen saturation (SaO₂) of ≤88% with or without hypercapnia confirmed 2 times over a 3-week period or
• PaO₂ between 55-60 mmHg (7.3-8 kPa) or SaO₂ of 88%, if there is evidence of pulmonary hypertension, peripheral edema suggesting CHF, or polycythemia (hematocrit >55%)

The aim of O₂ therapy is to increase baseline PaO₂ to ≥60 mmHg (8 kPa) and/or produce SaO₂ of ≥90%, thus preserving vital organ function. Reassessment using measurement of ABG, or O₂ saturation should be conducted 60-90 days after long-term O₂ therapy initiation.

Inappropriate use of O₂ therapy may result in respiratory depression. Patients must be given adequate instructions about the source of O₂ to be used, method of delivery, duration of use, and flow rates to be used for different levels of physical activity (eg at rest, during exercise, during sleep). Patients should be warned to discontinue smoking when prescribed O₂. 

NIV

NIV may be considered in patients with stable very severe COPD, especially those with pronounced chronic hypercapnia and a history of hospitalization, needing assisted ventilation during exacerbations. NIV improves lung function, clinical symptoms, quality of life, and survival, and reduces hospitalization rate. 

Lifestyle Modification

Smoking Cessation

Smoking cessation is the single most effective and cost-effective method to reduce the risk of developing COPD and to stop its progression.

Counseling may be employed to aid the patient and pharmacotherapies (eg Nicotine preparations, Bupropion, Nortriptyline, and Varenicline) may also be considered to aid smoking cessation.  

*Please see Smoking Cessation disease management chart for further information.

Patient Education

Patient education plays an important role in increasing the patient’s knowledge and understanding of the disease. It can also improve skills in symptom recognition, breathing and physical exercise, medication use including proper technique, and environmental modification. It is important to note that adherence to inhaled medications has been associated with reduced risk of death and hospital admission due to COPD exacerbations. Measures must be taken to reduce total personal exposure to tobacco smoke, occupational dust, chemicals, and air pollutants.  

Improving attitude towards nutrition and exercise, smoking cessation, quality of life factors, and coping skills (eg relaxation techniques, stress management) is essential. Improving patient responses to exacerbations and initiating discussions about end-of-life issues including advance directives are likewise important. Protective strategies for basic infection control such as washing hands, wearing a face mask, and face shield, and social distancing should be emphasized.  

Family-focused Health Education and Community Interventions  

A multidisciplinary healthcare team may help educate both the patients and their families on the short- and long-term care of COPD, provide action plans and anticipatory care, address psychosocial issues of families living with COPD, and sustain the patient's and family's motivation to adhere to COPD management.  

Community interventions help prevent and control COPD exacerbations by improving the community's awareness of the disease (eg community bulletins and broadcasts, information dissemination on environmental factors causing the disease, and formation of online support groups and community-based healthcare teams). 

Other Therapy

Pulmonary Rehabilitation  

Pulmonary rehabilitation is a multidisciplinary program for patients with chronic respiratory impairment that is individually designed to maximize a patient’s physical and social performance and autonomy. In regions with limited resources, simplified pulmonary rehabilitation programs are useful and are recommended.  

Pulmonary rehabilitation includes exercise training, nutrition counseling, education, and psychological support. It is recommended for symptomatic patients with an FEV1 of <50% predicted. It may also be considered in symptomatic patients with FEV1 of >50% predicted with exercise limitations, patients with an mMRC of >1, and following acute exacerbations. The program should last for 6-8 weeks to be effective, and no additional benefit is seen in extending the program to 12 weeks.  

In- or outpatient pulmonary rehabilitation is effective in improving clinically relevant outcomes; however, there are challenges encountered in the delivery (eg scarce in-person programs, COVID-19 pandemic). As an alternative, telerehabilitation (eg video conferencing, mobile application with feedback, telephone calls) has been proposed.

Surgery

Surgery may be considered in patients who have large bullae or severe COPD with marked functional impairment in spite of maximal medical treatment.

Surgical procedures for COPD include the following:

• Bronchoscopic lung volume reduction (BLVR): For patients with heterogenous emphysema
• Bullectomy: May be considered in patients with space-occupying bulla (at least 1/3 of hemithorax)
• Lung volume reduction surgery (LVRS): For patients with upper-lobe emphysema
• Lung transplantation: May be considered in patients with severe COPD with FEV₁ of <50% and breathlessness refractory to medical therapy, non-smoker, completed pulmonary rehabilitation, where bullectomy, BLVR, and LVRS are not applicable, and without any contraindications for transplantation

COPD Exacerbations

Site of Care

Please refer to Symptom/Risk Evaluation of COPD table for characteristics per patient category

Patients belonging to category A or B may be managed on an outpatient basis during exacerbations. Patients belonging to category E may require hospitalization and more aggressive management during exacerbations.

The following are the indications for hospital treatment for COPD exacerbations: 

• Significant increase in signs and symptoms (eg sudden development of resting dyspnea, SaO₂ of <90%, changes in chest X-ray, arterial pH of <7.35, arterial PaO₂ of <7 kPa, <53 mmHg)
• Acute respiratory failure
• Onset of new symptoms (eg cyanosis, peripheral edema, impaired level of consciousness)
• Absence of response to initial medical treatment
• Significant comorbidities (eg heart failure or newly occurring arrhythmias)
• Frequent exacerbations
• Older age
• Lack of home support

Assessment of Severity

To assess the severity of COPD exacerbation, history and symptoms, physical examination, and laboratory tests (including C-reactive protein [CRP]) findings are assessed.

During a physical examination, a dyspnea visual analog scale (VAS) is used to grade the patient’s dyspnea with a score of 0 being not short of breath, and a score of 10 as the worst shortness of breath the patient has experienced. Vital signs determination including respiratory rate and heart rate are also essential to assess the severity of the exacerbation.

Laboratory Tests  

ABG measurement results showing a PaO₂ of <8 kPa, <60 mmHg, and/or SaO₂ of <90% with or without PaCO₂ of >50 mmHg on room air is indicative of respiratory failure. If there are no facilities to measure blood gases, SaO₂ should be measured.

Chest X-ray is helpful in patients with suspected pneumonia. It may be useful in identifying alternative diagnoses that can mimic symptoms of exacerbation.  

Electrocardiogram (ECG) is helpful in diagnosing right ventricular hypertrophy, arrhythmias, and ischemic episodes. It aids in the diagnosis of pulmonary embolism from COPD, as right ventricular hypertrophy and large pulmonary arteries may lead to confusing radiographic and ECG findings.  

A complete blood count (CBC) may show polycythemia (hematocrit >55) or bleeding. White blood cells (WBC) may be elevated in patients with respiratory infection. According to studies, eosinophil counts can predict the effects of ICS in preventing exacerbations; however, the use of eosinophil counts should always be combined with the clinical assessment of exacerbation risks (eg previous history of exacerbations, ethnicity, smoking status, geographical location).  

Biochemical tests may be helpful in determining the cause of exacerbation and in diagnosing other comorbid conditions (eg electrolyte imbalances, diabetic crisis, poor nutrition, acid-base disorders).  

The presence of purulent sputum during an exacerbation is a sufficient basis for starting antibiotics. Culture and sensitivity testing of sputum must be done if the patient does not respond to the initial antibiotic therapy. 

Classification of the Severity of COPD Exacerbations  

Mild exacerbation is suspected in patients with the following:

• Dyspnea VAS of <5
• Respiratory rate of <24 breaths/minute
• Heart rate of <95 beats per minute (bpm)
• Resting SaO₂ of ≥92% breathing ambient air (or patient's usual O₂ prescription) and change of ≤3%
• CRP of <10 mg/L 

Moderate exacerbation is suspected in patients who meet ≥3 out of 5 criteria: 

• Dyspnea VAS of ≥5
• Respiratory rate of ≥24 breaths/minute
• Heart rate of ≥95 bpm
• Resting SaO₂ <92% breathing ambient air (or patient's usual O₂ prescription) and/or change of >3%
• CRP of ≥10 mg/L
• Hypoxemia (PaO₂ of ≤60 mmHg) and/or hypercapnia (PaCO₂ of >45 mmHg) without acidosis on ABG 

Severe exacerbation is suspected in patients with the following:

• Dyspnea, respiratory rate, heart rate, SaO₂, and CRP same as moderate exacerbation
• Hypercapnia (PaCO₂ of >45 mmHg) and acidosis (pH of <7.35) on ABG 

Pharmacological Therapy

Bronchodilators

Long-acting beta₂-agonist bronchodilators include Arformoterol, Bambuterol, Formoterol, Indacaterol, Olodaterol, Salmeterol, and Tulobuterol. Short-acting beta₂-agonist bronchodilators include Clenbuterol, Fenoterol, Hexoprenaline, Levalbuterol, Orciprenaline, Procaterol, Salbutamol (Albuterol), Terbutaline, and Trimetoquinol.

Long-acting anticholinergic bronchodilators include Aclidinium, Glycopyrronium, Tiotropium, and Umeclidinium. Short-acting anticholinergic bronchodilators include Ipratropium and Oxitropium.

Hospital Management

Short-acting inhaled beta₂-agonists, with or without short-acting anticholinergics, are typically preferred for treating acute COPD exacerbations. An anticholinergic may be added if the patient does not respond immediately to short-acting inhaled beta₂-agonists.

Long-acting bronchodilators can be used with or without ICS during an exacerbation or as a maintenance therapy that should be started as soon as possible before hospital discharge.

Home Management

The dose and/or frequency of ongoing bronchodilator treatment should be increased. An anticholinergic, if not yet in use, may be added until improvement is noted. A high-dose nebulized therapy may be given when required for several days. The long-term use of nebulizer therapy after an exacerbation is not recommended.

Corticosteroids

Corticosteroids improve oxygenation and lung function and reduce the risk of relapse, treatment failure, and length of hospital stay.

Hospital Management  

Oral or intravenous corticosteroids are recommended as an addition to bronchodilator therapy, in the absence of significant contraindications. The oral route is preferred, as no significant difference in efficacy was seen when compared to the parenteral administration. The intravenous route may be used in patients with severe exacerbation and with contraindications to oral medications.

Corticosteroids may shorten recovery time and help hasten the restoration of lung function. The duration of therapy with oral corticosteroids must not exceed 5 days, as there is no advantage to prolonged therapy and the risk of side effects is increased.  

Home Management  

The addition of oral corticosteroid to existing bronchodilator therapy may be considered if the patient’s baseline FEV₁ is <50% predicted. Nebulized Budesonide alone or in combination with Formoterol may be used as an alternative to oral corticosteroids as it may cause a significant reduction of complications (eg hyperglycemia). 

Antibiotics

Antibiotics are given to patients who present with increased purulence of sputum together with an increase in dyspnea and sputum volume or in patients who need mechanical ventilation. Antibiotics may reduce the recovery time, interval to relapse, treatment failure, and duration of hospital stay.

Local antibiotic sensitivity patterns for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis must be taken into account when choosing an antibiotic agent.

The recommended oral antibiotic agents include Amoxicillin, Doxycycline, and Clarithromycin as first-line; and Co-amoxiclav, Levofloxacin, Co-trimoxazole, Azithromycin, and Cefuroxime axetil as second-line and are given if no improvement is seen or with clinical deterioration after 72 hours of treatment initiation.

The recommended intravenous antibiotic agents include Co-amoxiclav, Clarithromycin, and Piperacillin/tazobactam. The recommended duration of antibiotic therapy is 5-7 days for hospitalized patients and ≤5 days for outpatient treatment of COPD exacerbations.

Heparin (SC/Low Molecular Weight)

Consider administration of SC or low molecular weight Heparin to reduce the risk of pulmonary embolism in patients with polycythemia or dehydration, with or without a history of thromboembolic disease. 

Other Therapy

O₂ Therapy  

O₂ therapy remains to be the cornerstone of hospital treatment for COPD exacerbations and in patients with chronic respiratory failure. The goal of O₂ therapy is to maintain SaO₂ of 88-92% without precipitating respiratory acidosis or worsening hypercapnia. An SaO₂ of >93% is not advisable as the patient may become drowsy from carbon dioxide (CO₂) retention. Once O₂ is started, ABG must be checked after 30-60 minutes to ensure adequate oxygenation without carbon dioxide retention or acidosis. Blood gases must be monitored regularly depending on the response to treatment.

Mechanical Ventilation

NIV  

NIV is the first-line treatment of acute hypercapnic respiratory failure in COPD exacerbation in patients without contraindications. It is usually employed in patients with ≥1 of the following: Severe dyspnea with signs of respiratory muscle fatigue, and/or increased work of breathing (eg use of accessory muscles, intercostal space retraction), acidosis (arterial pH ≤7.35 and/or PaCO₂ ≥6.0 kPa, 45 mmHg), or persistent hypoxemia despite supplemental O₂ therapy.

NIV has been shown to increase pH, reduce PaCO₂, reduce the severity of breathlessness in the first 4 hours of treatment, and decrease the length of hospital stay, mortality, and intubation rate.

Invasive Mechanical Ventilation

Invasive mechanical ventilation is utilized in patients with signs and symptoms of severe dyspnea, apnea with loss of consciousness, gasping for air, <50 beats/minute pulse rate with a loss of consciousness, severe ventricular arrhythmias, psychomotor agitation unresponsive to sedatives, altered mental status in spite of aggressive pharmacotherapy, or life-threatening hypoxemia unresponsive to NIV.

Other indications for invasive mechanical ventilation include severe hemodynamic compromise unresponsive to hydration and medications, massive aspiration, unable to suction respiratory secretions, with contraindications to or failed NIV, or impending or previous respiratory or cardiac failure.   There is a major risk of ventilator-associated pneumonia, barotrauma, and failure to wean in patients on invasive mechanical ventilation.

Hydration and Nutrition

Fluid balance and nutritional status must be monitored and maintained at an optimal level.