Jennifer Hofmann, MS, PA-C

Chronic obstructive pulmonary disease (COPD), which has variable severity, is preventable and treatable.

COPD primarily affects smokers over age 40 and is a leading cause of mortality worldwide and is predicted to be the third-leading cause of death by 2020.

Prevalence is estimated at 4% to 10% worldwide and about 6.4 % in the United States. In the primary-care setting, about 50% of patients with severe COPD remain undiagnosed. The global burden of COPD is expected to increase, because of continued exposure to COPD risk factors, as well as the aging population.

COPD is characterized by chronic and progressive core symptoms of cough with or without sputum production and dyspnea. The airflow limitation in COPD is caused by a combination of parenchymal destruction (emphysema) and small airway disease (obstructive bronchiolitis).  Treatment modalities are guided by disease severity, and goals should focus on decreasing exacerbations, improving quality of life, preventing hospitalizations, and reducing symptoms.

Concomitant comorbidities in patients with COPD also affect hospitalizations and outcome and should be treated appropriately. None of the current medications modify disease progression, which is the hallmark of COPD.

Obstructive lung disease is characterized by a FEV1/FVC ratio of less than 0.70. Patients with COPD have a spirometry classification (grade 1 to 4).

The Gold Initiative for Chronic Obstructive Lung Disease system, known as GOLD, also categorizes patients into 4 categories (A,B,C,D), based on core symptoms, including breathlessness, which are assessed using hospitalizations, risk of exacerbations, and standardized questionnaires.

Smoking cessation should be strongly encouraged and supported in patients who continue to smoke. Smoking cessation can be facilitated with non-pharmacologic and pharmacologic modalities. Pharmacotherapy for COPD centers on long- or short-acting bronchodilators, specifically adrenergic agonists, antimuscarinic drugs, and inhaled Beta

. Comparative efficacy of short-acting beta agonists and short-acting antimuscarinic agents is generally similar with similar tolerability.

Types of inhaler devices include dry powder inhalers, metered dose inhalers, nebulizers, and soft mist inhalers. Each delivery device provides similar efficacy, and the key factors in device selection are patient ability to use properly, cost, preference, and treatment setting.

Treatment for patients with COPD is generally based on the category and stage of severity. Patients with COPD in category A are minimally symptomatic and experience fewer than 1 exacerbations per year. These patients are prescribed a short-acting inhaled bronchodilator as needed. Short-acting bronchodilators reduce symptoms, and short-acting inhaled beta

agonists (albuterol, levalbuterol) can be used as needed, improve symptoms quickly, last for 4 to 6 hours, and modestly improve FEV1.

agonists are generally well tolerated at recommended dosages with an increased heart rate and tremors more common in higher dosages.  Short-acting antimuscarinic drugs, such as ipratropium, are usually dosed 3 to 4 times daily and also improve lung function and symptoms. Ipratropium should be used with caution in patients with narrow-angle glaucoma and prostatic hypertrophy.

Category B patients are more symptomatic and have 0 to 1 exacerbations per year.  Recommended pharmacotherapy for patients in category B includes daily use of a long-acting bronchodilator, either a long-acting beta

agonist (LABA) or long-acting inhaled antimuscarinic agents (LAMA), plus an inhaled short-acting bronchodilator as needed. LABAs include aformoterol, formoterol, indacaterol, olodaterol, salmeterol, and vilanterol, which are dosed either once or twice daily. Aformaterol is also available as a solution for nebulization. The LAMAs include aclidinium, glycopyrrolate, revefenacin, tiotropium, and umeclidinium. Both LABAs and LAMAs have similar efficacy for quality of life and symptom control, but LAMA may be more effective at reducing the exacerbation rate. For patients with inadequately controlled symptoms on 1 long-acting bronchodilator, the addition of a long-acting bronchodilator from the other class may improve symptoms.

The are conflicting data regarding the potential increase in cardiovascular risk with the initiation of LABAs or LAMAs in patients with COPD.

The Understanding Potential Long-Term Impacts on Function with Tiotropium trial and the ASCENT trial provide evidence against significant major adverse cardiovascular events.

For GOLD Category C patients, first line pharmacotherapy is daily use of LAMAs. Long-acting inhaled antimuscarinic agents include aclinidium bromide, glycopyrronium, tiotropium, and umeclinidium, which are administered once or twice daily. LAMAs reduce the risk of exacerbations and hospitalizations compared with LABAs.

In patients on a LAMA with repeated exacerbations, guidelines recommend the addition of a LABA (preferred) or an inhaled corticosteroid (ICS). LAMA plus LABA combinations are preferred, because they improve lung function and control mild exacerbations with a lower risk of pneumonia compared with ICS.

Category D patients have severe symptoms with recurrent exacerbations and hospitalizations. Initiating therapy with a LAMA alone or a LABA/LAMA combination is recommended and has been shown to decrease exacerbations and improve patient outcomes. The use of an ICS has been shown to increase the risk of developing pneumonia in these patients and is therefore not recommended as initial therapy. In patients with asthma/COPD overlap, the ICS/LABA may be the initial choice of therapy.

Eosinophilia may be used to guide this latter treatment initiative, though this is still under debate.

In Category D patients who are prescribed a LABA/LAMA combination with persistent exacerbations, it is reasonable to add an ICS or switch to LABA/ICS. However, this regime may not appropriately control exacerbations, and a LAMA may be needed.

There are also a number of pharmacologic considerations in patients using ICS/LABA/LAMA combination therapy who have persistent exacerbations. Oral roflumilast can be added in patients with FEV1 < 50% predicted especially if they have been hospitalized for an exacerbation. Roflumilast is a phosphodiesterase -4 (PDE4) inhibitor that reduces inflammation by inhibiting the breakdown of intracellular cyclic AMP.

It is used once daily as a maintenance oral medication to prevent exacerbations, but it has a modest efficacy on lung function.

Finally, oral azithromycin therapy either daily or 3 times per week can be added for repeated exacerbations despite recommended standard therapy.

COPD is a chronic, preventable, and treatable disease. The goal of treatment is to improve exercise tolerance and overall health status; prevent disease progression; prevent and treat exacerbations; and reduce symptoms. Smoking cessation should be strongly encouraged and supported for patients with COPD who continue to smoke. In addition, reduction in occupational and personal exposure to fumes, gases, and pollutants should be targeted. It is essential to individualize pharmacologic treatment regimens and provide instruction on the proper use of inhalation devices. Inhaler technique and clinical response should be reassessed at follow-up visits every 3 to 6 months in stable patients before adjusting pharmacological regimens.

. Updated June 6, 2018. Accessed February 20, 2018

American Lung Association. Trends in COPD (chronic bronchitis and emphysema): morbidity and mortality.

https://www.lung.org/assets/documents/research/copd-trend-report.pdf

. Published March 2013. Accessed January 28, 2020.

Montuschi P. Pharmacological treatment of chronic obstructive pulmonary disease.

Global initiative for chronic obstructive lung disease. Global Initiative for Chronic Obstructive Lung Disease, Inc website. goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdf. Published 2018. Accessed January 28, 2020.

Wang MT, Liou JT, Lin CW, et al. Association of cardiovascular risk with inhaled long-acting bronchodilators in patients with chronic obstructive pulmonary disease: a nested case-control study.

2018;178(2):229-238. doi: 10.1001/jamainternmed.2017.7720.

Singh S, Loke YK, Furberg CD. Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

2008;300(12):1439-1450. doi: 10.1001/jama.300.12.1439.

Tashkin D, Celli B, Senn S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease (UPLIFT trial).

2009;15(1);137-140. doi: 10.1016/S0873-2159(15)30121-5.

Wise RA, Chapman KR, Scirica BM, et al. Effect of aclidinium bromide on major cardiovascular events and exacerbations in high-risk patients with chronic obstructive pulmonary disease: the ASCENT-COPD randomized clinical trial.

2019;321(17):1693-1701. doi: 10.1001/jama.2019.4973.

Chong J, Karner C, Poole P. Tiotropium versus long-acting beta-agonists for stable chronic obstructive pulmonary disease.

2012;(9):CD009157. doi: 10.1002/14651858.CD009157.pub2.

Wedzicha JA, Banerji D, Chapman KR, et al. Indacaterol-blycopyrronium versus salmeterol-fluticasone for COPD.

2016;374(23):2222. doi: 10.1056/NEJMoa1516385.

Martinez FJ, Calverley PM, Goehring UM, Brose M, Fabbri LM, Rabe KF. Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial.

2015;385(9971):857-66. doi: 10.1016/S0140-6736(14)62410-7.

Rabe KF. Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease.

2011;163(1):53-67. doi: 10.1111/j.1476-5381.2011.01218.x.

Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD.

Herath SC, Normansell R, Maisey S, Poole P. Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD).

Articles

Clinical response and inhaler technique should be reassessed at follow-up visits before readjusting procedures.

Individualize COPD Pharmacologic Treatment Regimens

Jean Covino, DHSc, MPA, PA-C, is a clinical professor and director of didactic education at the Pace University-Lenox Hill Hospital PA Program-NYC in New York, New York.

Jennifer Hofmann, MS, PA-C, is an associate clinical professor at the Pace University-Lenox Hill Hospital PA Program-NYC.

Pneumococcal vaccination is an important part of preventive health care in adults 65 years and older and in some younger adults with certain medical conditions.

is a leading cause of pneumonia, and it is associated with other invasive diseases, including bacteremia, meningitis, and otitis media. Appropriate vaccination of adults effectively reduces invasive pneumococcal disease.

There are 2 types of vaccines: the pneumococcal conjugate vaccine (PCV) and the pneumococcal polysaccharide vaccine (PPSV). The PPSV vaccine contains 23 partially purified pneumococcal capsular polysaccharides serotypes, which are most commonly associated with invasive pneumococcal disease. The PPSV vaccine is recommended for all adults initially at 65 years and older. The PPSV is also indicated for certain adults younger than 65 years chronic medical conditions. Certain patients need both types of pneumococcal vaccines, and in these patients the PCV should generally be administered prior to the PPSV (see

). The PPSV protects 50% to 85% of relatively healthy adults from invasive pneumococcal disease.

The PCV vaccine contains 13 pneumococcal capsular polysaccharides covalently linked to a protein. This formulation increases mucosal immunity, which decreases nasopharyngeal carriage and increases antibody production in infants and young children. Specific indications for adults are based on age and medical indications (see

). In 2014, the Advisory Committee on Immunization Practices (ACIP) recommended the routine use of 13-Valent Pneumococcal Conjugate Vaccine

PCV13) in series with 23-valent pneumococcal polysaccharide vaccine

PPSV23) for all adults aged ≥65 years based on demonstrated PCV13 efficacy and safety against PCV13-type pneumonia among adults aged ≥65 years.

ACIP recognized that there would be a need to reevaluate this recommendation, because it was anticipated that PCV13 use in children would continue to reduce disease burden among adults. Consequently, after having reviewed the evidence accrued during the preceding 3 years, in June 2019, the ACIP voted to remove the recommendation for routine PCV13 use among adults aged ≥65.

Updated Recommendations for the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) and the 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23) Among Adults

People treated with immunosuppressive drugs, long-term systemic corticosteroids, and radiation therapy

2nd dose ≥ 5 years after first PPSV23 dose

*Based on shared clinical decision making

If PCV 13 has been given, then given PPSV23 ≥ 1 year after PCV13

If PCV 13 has been given, then given PPSV23 ≥ 1 year after PCV13 and ≥ 5 years after any PPSV23 at age < 65

1 dose ≥ 8 weeks after PCV13 and ≥ 5 years after any PPSV23 at < 65 years

Pneumococcal vaccination is an important part of preventive health care in adults 65 years and older and in some younger adults with certain medical conditions. 

What are the New Pneumococcal Vaccination Recommendations for Adults?

About 1 million adults in the United States are hospitalized for pneumonia every year, and 50,000 die from this disease.

Half of all immunocompetent adults hospitalized for severe pneumonia in the United States are between 18 and 57 years of age).

In the United States, pneumonia is 1 of the top ten most expensive conditions seen during inpatient hospitalizations. In 2013, pneumonia had an aggregate cost of nearly $9.5 billion for 960,000 hospital stays.

The American Thoracic Society (ATS) and the Infectious Disease Society of America (IDSA) recently updated clinical practice guidelines previously published in 2007.

The guidelines focus on patients in the United States who are not immunocompromised and have not recently traveled abroad.

Antibiotic recommendations for the treatment of community-acquired pneumonia (CAP) include coverage for the traditional pathogens

Chlamydia pneumonia, Haemophilus influenza, Legionella, Moraxella catarrhalis, Mycoplasma pneumonia, Staphylococcus aureus,

Widespread use of the pneumococcal conjugate vaccine has caused changes in the microbial etiology of CAP. There has been an increase in other etiologic agents including viruses

The following recommendations were published by the ATS and IDSA in October 2019 for the management of CAP:

Sputum gram stain and cultures are not recommended in adults with CAP managed in an outpatient setting.

Blood cultures are not recommended in adults with CAP managed in an outpatient setting.

If influenza is circulating in the community, testing with rapid molecular assay rather than an antigen test is recommended.

Serum procalcitonin levels are not recommended to determine the need for initial empiric antibiotic therapy.

When deciding the need for hospitalization, clinical judgment plus the results of a validated prognostic tool should be used. The Pneumonia Severity Index (

mdcalc.com/psi-port-score-pneumonia-severity-index-cap

mdcalc.com/curb-65-score-pneumonia-severity

Corticosteroids are not recommended routinely in adults with nonsevere or severe CAP.

Patients should be treated with antibiotics for at least 5 days and 7 days for MRSA or

. The duration should be guided by validated measures of clinical stability, including ability to eat, blood pressure, heart rate, normal mentation, oxygen saturation, respiratory rate, and temperature.

In adults whose CAP symptoms resolve within 5 to 7 days, follow-up chest imaging does not have to be obtained.

Here are antibiotic treatment regimens for CAP in adults in an outpatient setting:

1. Outpatient adults with comorbidities, such as alcohol; asplenia; chronic heart, lung, liver, or renal disease; or diabetes.

Beta-lactam: amoxicillin/clavulanate, 500 mg/125 mg or 875 mg/125 mg, twice a day, or 2,000 mg/125 mg, twice a day

Cephalosporin (cefpodoxime, 200 mg, twice a day, or cefuroxime axetil, 500 mg, twice a day)

Macrolide (azithromycin, 500 mg x1, then 250 mg x5, or clarithromycin, 500 mg, twice a day, or 1000 mg (extended-release) x1)

Doxycycline, 100 mg, twice a day (less data). Consider a loading dose of 200 mg.

Monotherapy with a respiratory quinolone (levofloxacin, 750 mg QD, Moxifloxcin 400 mg, daily, Gemifloxacin 320 md, daily

2. Previously healthy adults without comorbidities or risk factors for antibiotic-resistant pathogens:

Amoxicillin, 1 g, 3 times a day (higher doses target resistant

)                                                            OR

A macrolide: azithromycin, 500 mg x1, then 250 mg x5, or clarithromycin, 500 mg, twice a day, or 1000 mg (extended-release) x 1 (if local pneumococcal resistance is < 25%) Resistance in most of the United States is > 30%.

The evidence-based clinical practice guidelines were published to help clinicians optimize the care for patients with CAP based on new data. Antimicrobial therapy should be based on the presence of comorbidities and local resistance patterns. These recommendations delineate minimum clinical standard of care but were not developed to obviate the need for clinical observation.

, is a clinical professor and director of didactic education at the Pace University-Lenox Hill Hospital PA Program-NYC in New York, New York.

, is an associate clinical professor at the Pace University-Lenox Hill Hospital PA Program-NYC.

Top 20 Pneumonia Facts — 2018. American Thoracic Society website.

thoracic.org/patients/patient-resources/resources/top-pneumonia-facts.pdf

Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America.

American Journal of Respiratory and Critical Care Medicine

. 2019;200(7): e45-e67. doi: 10.1164/rccm.201908-1581ST.

ATS and IDSA update clinical practice guidelines for community-acquired pneumonia.

What Is the Best Outpatient Treatment for CAP in Adults?

Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder with multiple abdominal symptoms, including recurrent pain and altered bowel habits, such as constipation, diarrhea, or both. The prevalence of IBS in North America ranges from 10% to 16%, and it is most commonly diagnosed in young women between ages 20 and 30.

Patients with IBS are commonly seen in primary-care settings and referred to gastroenterologists for further evaluation and management.

There are no specific diagnostic markers for IBS, and the diagnosis is suggested in patients with chronic and recurrent abdominal pain and altered, fluctuating bowel habits without alarm features or “red flags,” such as advanced age, family history of bowel cancer or inflammatory bowel disease, rectal bleeding, and weight loss. The Rome criteria qualify and quantify current (within the past 3 months) core features of abdominal pain and altered bowels habits and are widely used to diagnose IBS. The differential diagnosis for IBS depends on the predominant symptom(s) and includes bacterial overgrowth, celiac disease, colorectal cancers, inflammatory bowel disease, and lactose intolerance. There is no cure for IBS, and its management should be individualized based on patient preferences, potential triggers, predominant symptoms, and symptom pattern and severity.

The goals of treatment are an improved quality of life and relief or significant improvement of core symptoms. Initial management of mild to moderate IBS includes patient education and dietary and lifestyle modifications. Clinician and patient interaction is important to establish patterns of daily bowel habits and symptom flare-ups, and monitor the symptom response to therapy. Many IBS patients have symptom flare-ups related to dietary changes, and a diary of symptoms and relationship to specific foods benefit from avoiding gas-producing foods, such as a low fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) diet. Gas-producing foods include legumes (beans) and cruciferous vegetables, such as broccoli, Brussels sprouts, cabbage, and cauliflower. Low FODMAPS diets exclude many foods that contain poorly absorbed carbohydrates, which ferment in the bowel and produce bloating and gas. FODMAPS containing foods are heterogeneous and include dairy products, a wide range of fruits, such as apples, cherries, mangoes, pears, and watermelon), and grains, such as barley, rye, and wheat. Short trials of gluten and lactose avoidance may reduce the symptoms of IBS patients.

Dietary fiber has a controversial role in IBS. Soluble fibers such as ispaghula, oats, or psyllium may improve overall IBS symptoms. Insoluble fibers, such as bran, may improve constipation but can worsen other IBS symptoms, such as bloating.

Encourage patients to increase water intake when gradually adding dietary fiber to reduce bloating and gas.

Pharmacologic therapy should be considered in moderate to severe IBS symptoms that do not significantly improve with lifestyle modifications. Treatment should focus on the patient’s predominant symptoms, such as constipation or diarrhea. IBS with constipation (IBS-C) should be managed with several weeks of soluble fiber. If that regimen is ineffective, polyethylene glycol (PEG) (17g up to 34 grams once daily) can be used. If constipation persists, medications such as lubiprostone or linaclotide can be used. Lubiprostone is a chloride channel activator that increases intestinal fluid secretion and is dosed at 8 mcg orally twice daily for IBS-C. The major adverse effect of lubiprostone is nausea. Linaclotide is a guanylate cyclase agonist that also increases intestinal fluid secretion. It is dosed at 290 mcg once daily for IBS-C. The major adverse effect of linaclotide is diarrhea. Both lubiprostone and linaclotide have demonstrated efficacy for IBS-C in randomized placebo-controlled clinical trials. However, the long-term safety of these drugs is unknown.

Patients with IBS-diarrhea (IBS-D) can benefit from antidiarrheal drugs, such as loperamide, which decreases stool frequency and improves consistency. Eluxadoline (100 mg orally twice daily) is an oral mixed opioid receptor agonist/antagonist that is also approved for IBS-D, with less constipation.

The most common adverse effects are constipation and nausea, and eluxadoline has been associated with pancreatitis in patients with biliary tract disorders. Eluxadoline is contraindicated in patients without a gallbladder and certain biliary tract diseases.

In patients with IBS with pain as the predominant symptom, there are a few therapeutic options. IBS patients with pain generally benefit from oral antispasmodic drugs, such as dicyclomine or hyoscyamine, which have antimuscarinic and smooth muscle relaxing effects on the colon. Antidepressants, specifically tricyclic antidepressants, such as amitriptyline, imipramine, and nortriptyline, can improve abdominal pain in IBS. Rifaximin is an oral antibiotic that has efficacy in patients with moderate to severe IBS with bloating. It can be used 3 times a day for 14 days, with demonstrable improvements in global IBS symptoms including bloating.

In terms of herbal medications and probiotics, such as bifidobacteria and lactobacillus, they are potentially effective for patients with IBS, but data from trials are conflicting. Several clinical trials demonstrate that peppermint oil, in capsule form taken orally 3 times daily reduces abdominal pain, bowel movements, distention, and flatulence.

IBS is a common recurrent GI disorder characterized by abdominal pain and discomfort, bloating, and bowel changes, such as constipation and/or diarrhea. The overall management includes establishing a strong patient clinician relationship; dietary modification, such as low-gas-forming foods; increased soluble fiber; and increased physical activity. Pharmacologic management is guided by the patients’ predominant symptom(s) and includes antispasmodics for pain, eluxadoline and loperamide for IBS-D, linaclotide and lubiprostone for constipation, PEG, and soluble fiber.

, is a clinical assistant professor in the Pace University-Lenox Hill Hospital Physician Assistant Program atâ€¨the College of Health Professions in New York.

, is the associate director and a physician assistant at the School of Health Sciences at Touro College in Bayshore, New York.

1. Yang J, Deng Y, Chu H, et al. Prevalence and presentation of lactose intolerance and effects on dairy product intake in healthy subjects and patients with irritable bowel syndrome.

2013;11(3):262-268.e1. doi: 10.1016/j.cgh.2012.11.034.

2. Vazquez-Roque MI, Camilleri M, Smyrk T, et al. A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function.

2013;144(5):903-911.e3. doi: 10.1053/j.gastro.2013.01.049.

3. Moayyedi P, Quigley EM, Lacy BE, et al. The effect of fiber supplementation on irritable bowel syndrome: a systematic review and meta-analysis.

2014;109(9):1367-74. doi: 10.1038/ajg.2014.195.

4. Drossman DA, Chey WD, Johanson JF, et al. Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome--results of two randomized, placebo-controlled studies.

2009;29(3):329-41. doi: 10.1111/j.1365-2036.2008.03881.x.

5. Rao S, Lembo AJ, Shiff SJ, et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation.

6. Viberzi [prescribing information]. Irvine, CA: Allergan USA, Inc; 2017. allergan.com/assets/pdf/viberzi_pi. Accessed December 28, 2017.

7. Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation.

2011;364(1):22-32. doi: 10.1056/NEJMoa1004409.

8. Grigoleit HG, Grigoleit P. Peppermint oil in irritable bowel syndrome.

There is no cure for IBS, and its management should be individualized based on patient preferences, potential triggers, predominant symptoms, and symptom pattern and severity. 

Jennifer Hofmann, MS, PA-C

Articles

Individualize COPD Pharmacologic Treatment Regimens

What are the New Pneumococcal Vaccination Recommendations for Adults?

What Is the Best Outpatient Treatment for CAP in Adults?

Management of Irritable Bowel Syndrome