Update on the Long-Term Treatment Of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD), also known as emphysema or chronic bronchitis, affects an estimated 15 million Americans and was the third-leading cause of death in the U.S. in 2011.[1] Smoking is responsible for 80 percent of COPD deaths.[2] Secondhand smoke, air pollution, exposure to workplace dusts and chemicals, a history of childhood respiratory infections, certain genetic traits, and poverty are other risk factors.[3]

Diagnosing COPD

COPD is a condition involving chronic inflammation and obstruction of the lungs' airways, making it difficult to breathe. It is diagnosed based on symptoms such as shortness of breath and a mucus-producing cough, as well as through a breathing test known as spirometry, which measures how well air flows through a patient's airways.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD), a collaboration between the National Heart, Lung, and Blood Institute and the World Health Organization launched in 1997, periodically updates its guidelines on diagnosing and treating COPD.[4] The 2015 GOLD guidelines classify the severity of COPD into four categories based on three factors: the presence of various symptoms, such as breathlessness; the degree of airway obstruction on spirometry; and the frequency of past COPD exacerbations.[5]

Treating COPD

COPD treatment aims to slow the decline in lung function, improve daily symptoms, increase exercise tolerance, and reduce the risk of exacerbations and death. (For the GOLD recommendations for first-choice COPD treatments,see table below.)[6]

Recommended First-Choice Treatments for COPD (Based on 2015 Guidelines)[16]

* Risk levels refer to the risk of a future exacerbation. Low-risk patients are those with mild to moderate airway obstruction on spirometry and less than two exacerbations per year, with no hospitalizations for exacerbations. High-risk patients are those with severe to very severe airway obstruction, two or more exacerbations per year, or at least one exacerbation requiring a hospitalization per year.[17]
** SABA (short-acting beta agonist), SAMA (short-acting muscarinic antagonist), LABA (long-acting beta agonist); LAMA (long-acting muscarinic antagonist), ICS (inhaled corticosteroid).

The mainstay of COPD treatment is a group of inhaled medications known as bronchodilators, which open up the lungs’ airways and make it easier to breathe. There are four categories of bronchodilators: short-acting beta agonists (SABAs), short-acting muscarinic antagonists (SAMAs), long-acting beta agonists (LABAs) and long-acting muscarinic antagonists (LAMAs). (See table below, for examples of specific drugs in these groups.)

SABAs and SAMAs are recommended for use as needed for low-risk patients with infrequent or mild symptoms. For all other COPD patients, regular therapy with LAMAs or LABAs is recommended.

Inhaled corticosteroids (ICSs) are another group of medicines for COPD; they work by reducing inflammation in the lungs. The GOLD guidelines recommend that an ICS be added to bronchodilators for high-risk patients.

For patients with persistent symptoms even after inhaled therapy, several oral medications, some of which have similar effects to bronchodilators, are recommended as options. But theophylline (ELIXOPHYLLIN, THEO-24, UNIPHYL), the most commonly used oral medication for COPD, is less effective and riskier than the inhaled drugs.[7]

Our take: Bronchodilators

Public Citizen’s Health Research Group agrees with the GOLD recommendations on bronchodilator use. However, there are specific bronchodilators that we recommend not be used.

Among the LABAs, we recommend against indacaterol (ARCAPTA NEOHALER) because the pre-approval studies did not establish an ideal dose that would minimize potential side effects.[8] We also recommend that olodaterol (STRIVERDI RESPIMAT) not be used for the first seven years after its 2014 approval, because new drugs often are withdrawn from the market or serious new adverse reaction warnings are added to their labeling within seven years after they have been approved by the Food and Drug Administration (FDA).

For the same reason, the only LAMA we currently recommend is tiotropium (SPIRIVA). However, there have long been concerns that tiotropium (and other LAMAs) may increase the risk of cardiovascular death,[9] especially the SPIRIVA RESPIMAT formulation.[10] We therefore recommend that you use only the SPIRIVA HANDIHALER version.

The two more recently approved LAMAs, aclidinium (TUDORZA PRESSAIR) and umeclidinium (INCRUSE ELLIPTA), should not be used until 2019 and 2021, respectively.

Two new drugs in a new category of inhaled medicines, combining a LABA and a LAMA, recently have been approved by the FDA for COPD. Because of lingering concerns over the combinations’ cardiovascular safety and the lack of evidence that they are more effective than simply taking individual LABAs and LAMAs together, we recommend that you not use the two currently approved LABA-LAMA combination drugs (see table below).

Our take: ICSs

Regarding ICSs, we are slightly more cautious than the GOLD guidelines in that we recommend that an ICS be added to bronchodilators only for high-risk patients with severe, persistent symptoms. This is because the benefit of adding an ICS to bronchodilators is not well established, and because ICSs have serious side effects, including pneumonia.[11]

The only ICS medications approved for COPD in the U.S. are marketed in combination with a LABA. Of the three LABA-ICS combination drugs (see table below), we recommend against vilanterol- fluticasone (BREO ELLIPTA) because in the pre-approval studies, fluticasone only increased risks, while adding little benefit over use of vilanterol alone.[12]

Inhaled and Oral Drugs for the Long-Term Treatment of COPD[18]

* Do Not Use (in the case of tiotropium, the Do Not Use classification applies only to the SPIRIVA RESPIMAT form)
** Do Not Use for Seven Years After Approval (olodaterol, 2021; aclidinium, 2019; umeclidinium, 2021; roflumilast, 2018)
*** Limited Use

Nondrug treatments

In addition to drugs, pulmonary rehabilitation therapy helps improve symptoms and quality of life. Such therapy involves exercise, nutritional counseling, breathing strategies, psychological counseling and education.[13] For patients with severe COPD and difficulty breathing even at rest, continuous oxygen therapy is lifesaving and is so far the only therapy proven to extend the lives of COPD patients.[14]

What You Can Do

If you have COPD and you smoke, stopping smoking is the single most important step you should take to improve your symptoms and prevent the disease from getting worse. You also should get the pneumococcal vaccine known as PPSV23 to prevent pneumonia and an annual influenza vaccine.[15] If you have severe COPD, you should be on oxygen therapy.

If you are at low risk for future exacerbations and do not have frequent symptoms, talk to your doctor about starting a SAMA or SABA inhaler, to be used as needed to relieve breathing trouble. If you have more frequent symptoms or are at high risk for a future exacerbation, you should instead take a regular LABA or LAMA.

Only if you are high-risk, and if your symptoms persist or worsen on a LAMA or LABA inhaler, should you consider adding an ICS. You should take the ICS at the lowest dose necessary to achieve some relief of your symptoms.

If you use an inhaler for COPD or asthma, you must learn its proper use. Poor technique can render an inhaler ineffective and, for ICS inhalers, increase the risk of such side effects as hoarseness, sore throat and oral thrush. To reduce these side effects, it also is very important to always rinse and gargle with water or mouthwash ("swish and spit") after using your ICS inhaler.

For a checklist on how to use an inhaler device correctly, visit http://bit.do/inhalers.

We recommend oral medications only in severe cases when a person does not respond to LABAs, LAMAs or LABA-ICS combination therapy.

If your breathing or other symptoms suddenly worsen, see your doctor immediately.

References

[1] Centers for Disease Control and Prevention. Chronic Obstructive Pulmonary Disease (COPD). Who has COPD? http://www.cdc.gov/copd/index.html. Accessed August 26, 2015.

[2]American Lung Association. Chronic Obstructive Pulmonary Disease (COPD) Fact Sheet. http://www.lung.org/lung-disease/copd/resources/facts-figures/COPD-Fact-Sheet.html#Prevalence?referrer=https://www.google.com/. Accessed August 18, 2015.

[3] Ibid.

[4] Global Initiative for Chronic Obstructive Lung Disease. Who Are We? http://www.goldcopd.org/about-us.html. Accessed August 19, 2015.

[5] Global Initiative for Chronic Obstructive Lung Disease. At-a-Glance Outpatient Management Reference for Chronic Obstructive Pulmonary Disease (COPD). Updated 2015. http://www.goldcopd.org/uploads/users/files/GOLD_AtAGlance_2015_Feb18.pdf. Accessed August 19, 2015.

[6] Ibid.

[7] Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Updated 2015. http://www.goldcopd.org/uploads/users/files/GOLD_Report_2015_Apr2.pdf. Accessed August 27, 2015.

[8] Public Citizen. Letter to FDA on indacaterol maleate (Arcapta Neohaler). March 16, 2011. http://www.citizen.org/hrg1938. Accessed August 27, 2015.

[9] Matera MG, Rogliani P, Cazzola M. Muscarinic receptor antagonists for the treatment of chronic obstructive pulmonary disease. Expert Opin Pharmacother. 2014;15(7):961-977.

[10] Public Citizen. Testimony Before the FDA's Pulmonary-Allergy Drugs Advisory Committee on Tiotropium (Spiriva Respimat). August 14, 2014. http://www.citizen.org/documents/2212.pdf. Accessed August 26, 2015.

[11] Nannini LJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;9:CD006829.

[12] Public Citizen. Letter to FDA Opposing Approval of Fluticasone Furoate/Vilanterol (FF/VI) for COPD. April 30, 2013. http://www.citizen.org/documents/2119.pdf. Accessed August 27, 2015.

[13] National Heart, Lung, and Blood Institute. What is Pulmonary Rehabilitation? http://www.nhlbi.nih.gov/health/health-topics/topics/pulreh. Accessed August 19, 2015.

[14] McDonald CF. Oxygen therapy for COPD. J Thorac Dis. 2014;6(11):1632 -1639.

[15] Centers for Disease Control and Prevention. 2015 Recommended Immunizations for Adults: By Health Condition. http://www.cdc.gov/vaccines/schedules/downloads/adult/adult-schedule- easy-read.pdf. Accessed August 27, 2015.

[16] Global Initiative for Chronic Obstructive Lung Disease. At-a-Glance Outpatient Management Reference for Chronic Obstructive Pulmonary Disease (COPD). Updated 2015. http://www.goldcopd.org/uploads/users/files/GOLD_AtAGlance_2015_Feb18.pdf. Accessed August 19, 2015.

[17] Ibid.

[18] Based on a search conducted on August 20, 2015 of the Food and Drug Administration’s prescription drug database, Drugs@FDA.

[19] Not FDA-approved for COPD, but recommended as first-choice therapies by the 2015 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and have long been used off-label in COPD patients. All other drugs in this table are FDA-approved for COPD.