Emphysema: Treatment & Medication

Treatment

Medical Care

Once the diagnosis of chronic obstructive pulmonary disease (COPD) is established, the patient should be educated about the disease and should be encouraged to participate actively in therapy. The goal of therapy is to relieve symptoms, prevent disease progression, improve exercise tolerance and health status, prevent and treat complications and exacerbations, and reduce mortality¹ Treatments should be added in a stepwise fashion to reach these goals.

Smoking cessation

Smoking cessation is the single most effective therapy for the majority of COPD patients.¹ A smoking cessation plan is an essential part of a comprehensive treatment plan. The success rates for smoking cessation are low because of the addictive potential of nicotine, the conditioned response to smoking-associated stimuli, psychosocial problems, and forceful promotional campaigns by the tobacco industry. The process of smoking cessation must involve multiple interventions.

Physician intervention

The transition from smoking to nonsmoking status involves 5 stages. These stages are (1) precontemplation, (2) contemplation, (3) preparation, (4) action, and (5) maintenance. Smoking intervention programs include self-help, group, physician-delivered, workplace, and community programs. Setting a target date to quit may be helpful. Physicians and other health care providers should participate in setting the target date and should follow up with respect to maintenance. Successful cessation programs usually use the following resources and tools:

• Patient education
• A target date to quit
• Follow-up support
• Relapse prevention
• Advice for healthy lifestyle changes
• Social support systems
• Adjuncts to treatment (ie, pharmacological agents)

According to the US Preventive Services Task Force guidelines, clinicians should ask all adults about use of tobacco products and provide cessation interventions to current users. The guideline engages a “5-A” approach to counseling that includes the following⁸ :

• Ask about tobacco use.
• Advise to quit through personalized messages.
• Assess willingness to quit.
• Assist with quitting.
• Arrange follow-up care and support.

Brief behavioral counseling and pharmacotherapy are each effective alone, although they are most effective when used together. The task force also advises clinicians to ask all pregnant women, regardless of age, about tobacco use. Those who currently smoke should receive pregnancy-tailored counseling supplemented with self-help materials.

Pharmacologic intervention

Supervised use of pharmacologic agents is an important adjunct to self-help and group smoking cessation programs. Nicotine is the ingredient in cigarettes primarily responsible for the addiction of smoking. Withdrawal from nicotine may cause unpleasant adverse effects (ie, anxiety, irritability, difficulty concentrating, anger, fatigue, drowsiness, depression, and sleep disruption). These effects usually occur during the first weeks after quitting smoking. Nicotine replacement therapies after smoking cessation reduce withdrawal symptoms. A person who smokes and who requires the first cigarette within 30 minutes of waking is likely to be highly addicted and would benefit from nicotine replacement therapy. Several nicotine replacement therapies are available.

Nicotine polacrilex is a chewing gum and produces better quit rates than counseling alone. Transdermal nicotine patches are readily available for replacement therapy. Long-term success rates have been 22-42%, compared with 2-25% with placebos. These agents are well tolerated, and the adverse effects are limited to localized skin reactions. The use of an antidepressant medication, bupropion (Zyban) (150 mg bid) has been shown to be effective for smoking cessation and may be used in combination with nicotine replacement therapy.

The most recent drug to receive approval for smoking cessation is varenicline (Chantix). Varenicline is a partial agonist selective for alpha4, beta2 nicotinic acetylcholine receptors. Action is thought to result from activity at a nicotinic receptor subtype, where its binding produces agonist activity while simultaneously preventing nicotine binding. Agonistic activity is significantly lower than nicotine.

Pharmacologic therapy for emphysema

Bronchodilators

Bronchodilators are the backbone of any COPD treatment regimen. They work by dilating airways and thereby decreasing airflow resistance. This increases airflow and decreases dynamic hyperinflation. Lack of response of pulmonary function testing should not preclude their use. These drugs provide symptomatic relief but do not alter disease progression or decrease mortality.

Short-acting bronchodilators

The 2 classes of short-acting bronchodilators are beta2 agonist and anticholinergic agents. Beta2 agonists stimulate beta2 adrenergic receptors, increasing cyclic adenosine monophosphate (cAMP) and resulting in bronchodilation. The inhaled route is preferred because it minimizes adverse systemic effects. The adverse effects are predictable and include tachycardia and tremors. Although rare, they may also precipitate a cardiac arrhythmia. Anticholinergic agents block M2 and M3 cholinergic receptors and result in bronchodilation. These agents are poorly absorbed systemically and are relatively safe. Reported adverse effects include dry mouth, metallic taste, and prostatic symptoms.

The initial choice of agent remains in debate. Historically, beta2 agonists were considered first line and anticholinergics added as adjuncts. Not surprisingly, studies have shown combination therapy results in greater bronchodilator response and provides greater relief.⁹ Monotherapy with either agent and combination therapy with both are acceptable options. The adverse effect profile may help guide therapy.

Long-acting bronchodilators

If short-acting agents do not provide sufficient relief, patients should be placed on a long-acting bronchodilator. Like the short-acting agents, the choices include long-acting beta agonists or long-acting muscarinic agents. In general, neither agent is preferred over the other. Oral phosphodiesterase inhibitors such as theophylline also provide long-acting bronchodilation, although their use is currently limited.

Long-acting beta-agonists include salmeterol, formoterol, and arformoterol. They all require twice-daily dosing. Multiple studies have demonstrated the benefit and safety of long-acting beta-agonists. The Toward a Revolution in COPD Health (TORCH) trial studied salmeterol with and without fluticasone versus placebo.¹⁰ It demonstrated decreased exacerbation rates, improved lung function, and improved quality of life. The TORCH trial showed a trend towards mortality benefit with salmeterol alone and salmeterol plus fluticasone.

Tiotropium was introduced in 2004 and is the only available long-acting muscarinic agent at this time. Tiotropium has been shown to provide 24-hour bronchodilation and is dosed once daily.¹¹ The Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial studied the effects of use over a 4-year period.¹² the UPLIFT trial showed improvements in lung function, quality of life, and exacerbations but did not show a decrease in the rate of decline of lung function.

Evidence is mounting of the efficacy of tiotropium over long-acting beta-agonists. Two large randomized trials have compared tiotropium, salmeterol, and placebo.^13,14 Both studies showed greater improvement in lung function, dyspnea, and quality of life in the tiotropium group versus the salmeterol group. The study by Brusasco et al also showed a delay in first exacerbations and fewer exacerbations per year in the tiotropium group.

Phosphodiesterase inhibitors increase intracellular cAMP and result in bronchodilation. Theophylline is a nonspecific phosphodiesterase inhibitor and is now limited to use as an adjunctive agent. Theophylline has a narrow therapeutic window with significant adverse cardiac effects. It is reserved for patients with hard-to-control COPD or for individuals who are not able to use inhaled agents effectively. Cilomilast and roflumilast are second-generation, selective phosphodiesterase-4 inhibitors. They cause a reduction of the inflammatory process (macrophages and CD8⁺ lymphocytes) in patients with COPD. Twice-daily dosing has been found to be clinically effective. The preliminary clinical studies suggest a favorable effect.

Roflumilast, a phosphodiesterase-4 inhibitor currently under investigation for use in the United States, exhibits anti-inflammatory effects, including reduced airway inflammation and improved lung function in patients with COPD. To analyze the impact of roflumilast on the incidence of COPD exacerbations requiring corticosteroids, Calverley et al performed 2 randomized, double-blind, placebo-controlled multicenter trials. Patients with COPD were randomly assigned to receive roflumilast or placebo for 52 weeks. Both studies revealed increased FEV₁ in patients who received roflumilast compared with placebo (P <.0001). In addition, the rate of COPD exacerbations was reduced by 17% in patients who received roflumilast compared with placebo (P <.0003).¹⁵

Anti-inflammatory therapy

Inflammation plays a significant role in the pathogenesis of COPD. Oral and inhaled corticosteroids attempt to temper this inflammation and positively alter the course of disease. The use of oral steroids in the treatment of acute exacerbations is widely accepted and recommended, given their high efficacy. On the other hand, use of oral steroids in the management of stable chronic COPD is not recommended, given their adverse effects. Inhaled corticosteroids, similar to other inhaled agents, are only minimally absorbed and therefore systemic adverse effects are limited. Nonsteroidal antiinflammatory drugs such as cromolyn and nedocromil have not been shown to be efficacious in the treatment of COPD.¹

Inhaled corticosteroids are widely used in COPD patients despite limited evidence of benefit. Despite the theoretical benefit, the current consensus is that inhaled corticosteroids do not decrease the decline in FEV₁ ¹ They have, however, been shown to decrease the frequency of exacerbations and improve quality of life for symptomatic patients with an forced expiratory volume in 1 second (FEV₁) of less than 50%.¹⁶ Inhaled corticosteroids are not recommended as monotherapy and should be added to a regimen that already includes a long-acting bronchodilator.

Oral steroids have been widely used in the treatment of acute exacerbation of COPD. A meta-analysis concluded that oral or parenteral corticosteroids (1) significantly reduced treatment failure and need for additional medical treatment and (2) increased the rate of improvement in lung function and dyspnea over the first 72 hours.¹⁷ The use of oral steroids in persons with chronic stable COPD is widely discouraged given the adverse effect profile, which includes hypertension, glucose intolerance, osteoporosis, fractures, and cataracts, among others. A Cochrane review showed no benefit at low-dose therapy and short-lived benefit with higher doses (>30 mg of prednisolone).¹⁸

Debate continues regarding use of inhaled corticosteroids and the risk for pneumonia in patients with COPD. Sin et al analyzed data from 7 large clinical trials (n = 7042) of patients with stable COPD who used inhaled budesonide (n = 3801) or a control regimen (placebo or formoterol alone). No significant difference was recorded for pneumonia occurrence between the budesonide group (3%; n = 122) and the control group (3%; n = 103). Increasing age and decreasing percent of predicted FEV₁ were the only variables that were significantly associated with pneumonia occurrence.¹⁹

Antibiotics

In patients with COPD, chronic infection or colonization of the lower airways with S pneumoniae, H influenzae, and/or Moraxella catarrhalis is common. Patients with severe disease have a higher prevalence of Gram-negative organisms such as Pseudomonas. The use of antibiotics for the treatment of acute exacerbations is well supported.² The patients who benefited most from antibiotic therapy were those with exacerbations that were characterized by at least 2 of the following: increases in dyspnea, sputum production, and sputum purulence (The Winnipeg criteria). No evidence supports the continuous or prophylactic use of antibiotics to prevent exacerbations.

Mucolytic agents

Viscous lung secretions in patients with COPD consist of mucus-derived glycoproteins and leukocyte-derived DNA. Mucolytic agents reduce sputum viscosity and improve secretion clearance. Although mucolytic agents have been shown to decrease cough and chest discomfort, they have not been shown to improve dyspnea or lung function.²⁰

Proton pump inhibitors

Sasaki et al conducted a randomized, observer-blind, controlled trial to determine if proton pump inhibitors (PPIs) reduce the incidence of common colds in patients with COPD. Patients (n = 100) were assigned to conventional therapy (control group) or conventional therapy plus PPI (lansoprazole 15 mg/d). The frequency of common colds and COPD exacerbations was measured, and the number of exacerbations per person over 12 months was significantly lower in the PPI group compared with the control group (P <.001). No significant difference in the numbers of common colds was observed between the PPI group and the control group. The authors concluded that although lansoprazole showed a significant decrease in COPD exacerbations, more definitive clinical trials are required.²¹

Oxygen therapy

Chronic hypoxemia may develop in patients with severe stable COPD (GOLD stage IV). Two landmark trials, the British Medical Research Council (MRC) study and the National Heart, Lung, Blood Institute's Nocturnal Oxygen Therapy Trial (NOTT) showed that long-term oxygen therapy improves survival by 2-fold or more in hypoxemic patients with COPD. Hypoxemia was defined as a PaO₂ of less than 55 mm Hg or oxygen saturation of less than 90%. Exercise-induced hypoxemia is also an accepted indication for supplemental oxygen because it improves exercise performance.

Oxygen toxicity from high inspired concentrations (>60%) is well recognized. Little is known about the long-term effects of low-flow oxygen. The increased survival rate and quality-of-life benefits of long-term oxygen therapy outweigh the possible risks. PaCO₂ retention from depression of the hypoxic drive has been overemphasized. PaCO₂ retention more likely is a consequence of ventilation/perfusion mismatching than of respiratory center depression. While this complication is not common, it can be avoided by titrating oxygen delivery to maintain the PaO₂ at 60-65 mm Hg.

The continuous-flow nasal cannula is the standard means of oxygen delivery for stable hypoxemic patients. The cannula is simple, reliable, and generally well tolerated. Each liter of oxygen flow adds 3-4% to the fraction of inspired oxygen (FIO₂). Oxygen-conserving devices function by delivering all of the oxygen during early inhalation. These devices improve the portability of oxygen therapy and reduce the overall costs. Three distinct oxygen-conserving devices are available, and they include reservoir cannulas, demand-pulse delivery devices, and transtracheal oxygen delivery. Transtracheal oxygen delivery involves insertion of a catheter percutaneously between the second and third tracheal interspace. Transtracheal oxygen delivery is invasive and requires special training for the physician, patient, and caregiver. The procedure has risks and medical benefits but is of limited applicability.

Vaccination

Infections can lead to COPD exacerbations. Vaccinations are a safe and effective modality to reduced infections in susceptible COPD patients. The pneumococcal vaccine should be offered to all patients older than 65 years or patients of any age who have an FEV₁ of less than 40% of predicted. The influenza vaccine should be given annually to all COPD patients.

Alpha1-antitrypsin deficiency

The treatment strategies for alpha1-antitrypsin (AAT) deficiency involve reducing the neutrophil elastase burden, primarily by smoking cessation, and augmenting the levels of AAT. Available augmentation strategies include pharmacologic attempts to increase endogenous production of AAT by the liver (ie, danazol, tamoxifen) or administration of purified AAT by periodic intravenous infusion or by inhalation. Tamoxifen can increase endogenous production of AAT to a limited extent, so this may be beneficial in persons with the PISZ phenotype.

Intravenous augmentation therapy is the only available approach that can increase serum levels to greater than 11 mmol/L, the protective threshold. Studies show that the infusions can maintain levels of more than 11 mmol/L, and replacement is administered weekly (60 mg/kg), biweekly (120 mg/kg), or monthly (250 mg/kg). The ability of intravenous AAT augmentation to alter the clinical course of patients with AAT deficiency has not been demonstrated. Uncontrolled observations of patients suggest that the FEV₁ may fall at a slower rate in patients who receive AAT replacement.²²

Surgical Care

Various surgical approaches to improve symptoms and restore function in patients with emphysema have been described. These should be offered to carefully selected patients as they may provide great benefit.

Bullectomy

Removal of giant bullae has been a standard approach in selected patients for many years. Bullae can range from a few centimeters to occupying a third of the hemithorax. Giant bullae may compress adjacent lung tissue, reducing the blood flow and ventilation to the relatively healthy lung. Removal of these bullae may result in expansion of compressed lungs and improvement of lung function. Giant bullectomy can produce subjective and objective improvement in selected patients, ie, those who have bullae that occupy at least 30%—and preferably 50%—of the hemithorax that compress adjacent lung, with an FEV₁ of less than 50% of predicted and relatively preserved lung function otherwise.

Lung volume reduction surgery

Lung volume reduction surgery (LVRS) attempts to decrease hyperinflation by surgically resecting the most diseased parts of the lung. This improves airflow by increasing the elastic recoil of the remaining lung and the mechanical efficiency of the respiratory muscles to generate expiratory pressures. The National Emphysema Treatment Trial (NETT) compared LVRS with medical management over a 4-year period.²³ Subgroup analysis revealed the greatest benefit was achieved for patients with upper lobe–predominant emphysema and low exercise tolerance. These patients had improvement in mortality, work capacity, and quality of life. LVRS was shown to improve mortality in subjects considered to be high-risk patients (eg, FEV₁ <20% predicted and either DLCO <20% predicted or homogeneous changes on chest CT scan).

Lung transplantation

COPD makes up the largest single category of patients who undergo lung transplantation. Lung transplantation provides improved quality of life and functional capacity but does not result in survival benefit. The lack of survival benefit makes the timing of transplant difficult. The patients selected to receive transplants should have a life expectancy of 2 years or less. Current guidelines by the International Society of Heart and Lung Transplantation recommends referring for transplantation when the BODE (body mass index, obstruction [FEV₁], dyspnea [ie, Medical Research Council Dyspnea Scale], and exercise capacity [ie, 6-min walking distance) index is greater than 5.²⁴

Consultations

Consultation with a pulmonary specialist is recommended.

Diet

Inadequate nutritional status associated with low body weight in patients with COPD is associated with impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity, and higher mortality rates. Nutritional support is an important part of their comprehensive care.

Medication

Oral and inhaled medications are used for patients with stable emphysema to reduce dyspnea and improve exercise tolerance. Most of the medications used in emphysema treatment are directed at the 4 potentially reversible mechanisms of airflow limitation: (1) bronchial smooth muscle contraction, (2) bronchial mucosal congestion and edema, (3) airway inflammation, and (4) increased airway secretions.

Bronchodilators

These agents decrease muscle tone in both the small and large airways of the lungs, thereby increasing ventilation. This category beta-adrenergic agents, methylxanthines, and anticholinergics.

Albuterol (Proventil, Ventolin)

Beta2 agonist that relaxes bronchial smooth muscle by action on beta2 receptors, with little effect on cardiac muscle contractility. Most patients (even those who have no measurable increase in expiratory flow) benefit from treatment. Inhaled beta-agonists initially are prescribed as needed. Frequency may be increased. Institute regular schedule in patients on anticholinergic drugs who remain symptomatic. Available as liquid for nebulizer, metered-dose inhalers (MDIs), and dry-powder inhalers.

Metaproterenol (Alupent)

Relaxes bronchial smooth muscle by action on beta2 receptors, with little effect on cardiac muscle contractility. Most patients (even those who have no measurable increase in expiratory flow) benefit from treatment. Inhaled beta-agonists initially are prescribed as needed. Frequency may be increased. Institute regular schedule in patients on anticholinergic drugs who remain symptomatic. Available as liquid for nebulizer, MDIs, and dry-powder inhalers.

Levalbuterol (Xopenex)

Used for treatment or prevention of bronchospasm. A selective beta2-agonist agent. Albuterol is a racemic mixture, while levalbuterol contains only the active R- enantiomer of albuterol. The S-enantiomer does not bind to beta2-receptors, but may be responsible for some adverse effects of racemic albuterol, including bronchial hyperreactivity and reduced pulmonary function during prolonged use.

Ipratropium (Atrovent)

Chemically related to atropine. Has antisecretory properties, and, when applied locally, inhibits secretions from serous and seromucous glands lining the nasal mucosa. Used on a fixed schedule with a beta-agonist.

Salmeterol (Serevent)

By relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, salmeterol can relieve bronchospasm. Effect also may facilitate expectoration. May be useful when bronchodilators are used frequently. More studies are needed to establish the role for these agents. When administered at high or more frequent doses than recommended, incidence of adverse effects is higher. The bronchodilating effect lasts >12 h. Used on a fixed schedule in addition to regular use of anticholinergic agents.

Formoterol (Oxis, Foradil)

Currently not available in the United States (investigational beta-agonist with rapid onset and long duration of action). By relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, it can relieve bronchospasms. Effect also may facilitate expectoration.
Shown to improve symptoms and morning peak flows in asthma. May be useful when bronchodilators are used frequently. More studies are needed to establish the role for these agents.
When administered at high or more frequent doses than recommended, incidence of adverse effects is higher. The bronchodilating effect lasts >12 h. Used on a fixed schedule in addition to regular use of anticholinergic agents.

Tiotropium (Spiriva)

A quaternary ammonium compound. Elicits anticholinergic/antimuscarinic effects with inhibitory effects on M₃ receptors on airway smooth muscles, leading to bronchodilation. Available as cap dosage form containing a dry powder for oral inhalation via HandiHaler inhalation device. Helps COPD patients by dilating narrowed airways and keeping them open for 24 h.

Theophylline (Aminophylline, Theo-24, Theo-Dur, Slo-bid)

Potentiates exogenous catecholamines. Stimulates endogenous catecholamine release and diaphragmatic muscular relaxation, which stimulates bronchodilation.
Popularity has decreased because of narrow therapeutic range and frequent toxicity. Bronchodilation may require near-toxic (>20 mg/dL) levels. However, clinical efficacy is controversial, especially in the acute setting.
Shown to increase exercise capacity, decrease dyspnea, and improve gas exchange. A longer-acting agent is used qd or bid.
Target concentration is 5-10 mcg/mL. Dosing = (target concentration - current level) X 0.5 (ideal body weight). Alternatively, 1 mg/kg results in approximately a 2-mcg/mL increase in serum levels.

Corticosteroids

These agents attempt to moderate the inflammatory component of COPD. They should only be added to a regimen that includes a long-acting bronchodilator.

Fluticasone (Flovent, Cutivate, Flonase)

Has extremely potent vasoconstrictive and anti-inflammatory activity. Has weak inhibitory effects on HPA axis when used at high doses for prolonged periods of time. Effectiveness is not established in COPD.

Budesonide (Pulmicort Turbuhaler)

Has extremely potent vasoconstrictive and anti-inflammatory activity. Has weak inhibitory effects on HPA axis when used at high doses for prolonged periods of time. Effectiveness is not established in COPD.

Smoking cessation therapies

Most effective when used in conjunction with a support program (ie, counseling, group therapy, and behavioral therapy).

Bupropion is used as a nonnicotine aid to smoking cessation. One study demonstrated 23% sustained cessation with bupropion tablets at 1 year, compared with a 12% sustained cessation with placebo. Bupropion also may be effective in patients who do not quit with nicotine replacement therapy.

Varenicline (Chantix) is a partial agonist selective for alpha4, beta2 nicotinic acetylcholine receptors. It is used in conjunction with support groups and/or behavioral counseling. Gradually increase dose upward within 1 wk before quit date to 1 mg PO bid pc. Decrease dose with severe renal impairment or end-stage renal disease

Nicotine transdermal system (Nicotrol, Habitrol, NicoDerm CQ)

Individuals who smoke >1 pack/d initially need a 21-mg patch followed by 14- and 7-mg patches.

Nicotine polacrilex (Nicorette)

Nicotine is absorbed through oral mucosa. Quickly absorbed and closely approximates time course of plasma nicotine levels observed after cigarette smoking.
Available as 2- or 4-mg gum in box containing 96 pieces. Careful adherence to chewing instructions is important for effective use. Manufacturer recommends that gum not be used longer than 6 mo.
Individual who smokes 1 pack/d should use 4-mg pieces. The 2-mg pieces are to be used by individuals who smoke <1 pack/d. Instruct patient to chew hourly and for initial cravings for 2 wk, then gradually reduce amount chewed over 3 mo.

Bupropion (Zyban)

Used in conjunction with a support group and/or behavioral counseling. Inhibits neuronal dopamine reuptake in addition to being a weak blocker of serotonin and norepinephrine reuptake.

Varenicline (Chantix)

Partial agonist selective for alpha4, beta2 nicotinic acetylcholine receptors. Action is thought to be the result of activity at a nicotinic receptor subtype where its binding produces agonist activity, while simultaneously preventing nicotine binding. The agonistic activity is significantly lower than nicotine. Also elicits moderate affinity for 5-HT3 receptors. Maximum plasma concentrations occur within 3-4 h after oral administration. Following regular dosing, steady state is reached within 4 d.

Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Amoxicillin (Amoxil, Trimox, Moxatag)

Interferes with synthesis of cell wall mucopeptides during active multiplication resulting in bactericidal activity against susceptible bacteria

Doxycycline (Doryx, Monodox, Doxy, Adoxa)

Broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. Almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations.
Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. May block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Sulfamethoxazole and Trimethoprim (Co-Trimoxazole, TMP-SMZ)

Inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid, resulting in inhibition of bacterial growth. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa. Like tetracycline, it has in vitro activity against Bartonella pertussis. Not useful in mycoplasmal infections.

Azithromycin (Zithromax)

These agents are replacing erythromycin as therapy for community-acquired pneumonia. They cover most potential etiologic agents, including Mycoplasma. The newer macrolides offer decreased GI upset and potential for improved compliance through reduced dosing frequency. They also afford improved action against Haemophilus influenzae.

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