Mercy Family Practice SC

Asthma

Table of Contents

Introduction

Asthma is a chronic inflammatory disease that is characterized by inflammation of bronchioles which them become hypersensitive which results in smooth muscle contraction and reduction in the diameter of the airways. This results in increased resistance to flow which results in air trapping and wheezing. In some cases, Asthma is due to allergens in the environment. This is referred to as extrinsic asthma. In most cases, the cause is unknown. This is referred to as intrinsic asthma.

Chronic Obstructive Pulmonary Disease (COPD) is another lung disease that is often caused by smoking. Air pollutions, occupational exposure and passive smoke inhalation may contribute. There are a minority of cases that are idiopathic (no known reason). As the name implies, the pathophysiology of COPD is similar to Asthma in that there is inflammation, bronchospasm, resistance to airflow, air trapping, and wheezing. For decades physicians made a distinction between the two. Asthma in the purest sense was considered a reversible airway disease of both large and small airways where prudent use of broncodilators known as short acting beta agonists (SABA) or inhaled corticosteroids (ICS) could return the airway back to normal. COPD in its purest case is considered a fixed loss in small air cells in which SABA or ICS will not return normal lung function, although they do help to maximize what reduced lung function is left. Asthma often starts in childhood or young adulthood where COPD often starts after 30 years of cigarette smoking.

However, there is now mounting evidence that Asthma is not a stable and fully reversible disease as once thought. It turns out that there is a lot of overlap between Asthma and COPD[1]. It is now thought that it may be the same disease manifest as a spectrum with Asthma on the one hand and COPD on the other. It is now referred to as Asthma-COPD Overlap Syndrome (ACOS). Treatment is similar in both groups and the guidelines for treatment in one is often applied for the other. For example, for decades steroids were reserved for Asthmatics and rarely used in COPD. However, over the years, clinicians looked at the patient clinically, and often added ICS regardless of these distinctions. Now we have literature that supports what we have been doing clinically for years.

Figure 1, Natural Progression of COPD & Asthma

Figure 1

The progression of COPD & Asthma are considered similar. They both show a loss in function over time & both are episodic. COPD tends to not return to baseline; however, Asthma comes close after each exacerbation.

The far left shows the pathophysiology of COPD and on the far right that of Asthma. In the center left is the natural progression of the disease over time with Forced Expiratory Volume in one second (FEV1) on the y-axis, and age on the x-axis. In the center right is a similar graph showing the natural progression of Asthma. You should notice the similarity of each disease which are virtually indistinguishable. COPD is characterized by marked drop in lung function with each exacerbation where Asthma tends to return to its former baseline. In spite of these distinctions, both show an unrelenting deterioration over time.

Emphysema may be considered a severe case of COPD in which so many air cells (alveoli) have been lost that air exchange has been compromised between the inhaled air and the blood stream. Clinically this is manifest by reduced oxygenation of the blood stream. This can be measured either as oxygen in the blood directly through a blood gas sample, or it can be measured indirectly through the wavelength of oxygen through an oximeter, which is a hand held device. The normal range of the partial pressure of oxygen (PaO2) is 75 - 100 mmHg, and for oxygen saturation, is 97 to 100%. You can also get a measure of diffusing capacity across the alveoli membrane using carbon monoxide through a pulmonary function test called the diffusing capacity (DLCO). A normal range is 80-100%.

Chronic bronchitis is a form of COPD with emphysema in which there is an excessive amount of mucous secretions. These patients were often described as “blue bloaters” in which they became cyanotic from reduced air exchange along with mucous plugging from excessive secretions.

Diagnosis

In general a patient with Asthma experiences tightness in the chest associated with shortness of breath, coughing or wheezing. If certain symptoms are present then they suggest a diagnosis of Asthma. These include: a patient who has recurrent attacks of wheezing; a person who has symptoms at night while recumbent; a person who has symptoms after exercise, a person who has symptoms following exposure to airborne allergens or pollutants; a person who has symptoms following an Upper Respiratory Infection (URI) which do not resolve after 10 days and persist for more than 6 weeks; and a person whose symptoms improve or resolve following treatment with bronchodilators.

Pulmonary function tests are the gold standard for making the diagnosis. Often the patient is sent to the hospital to have formal testing done. The patient breaths into a machine. They are often asked to take a deep breath, and then blow out has hard and as long as they can. Then they are asked to inhale, and repeat the process, perhaps three or four times. The process of often repeated after administering a short acting beta agonist (SABA). Several measurements are taken;

Table 1. Spirometry Values

ValueDefinition
FEV1:Forced Expiratory Volume in 1 second in Liters
FVC:Forced Vital Capacity in Liters
FEV1/FVC:The ratio of FVC1 divided by FVC
FEF25-75:Forced Expiratory Flow in the 25 to 75% of flow

Flow is defined as the change of volume divided by time (V/t). A flow volume loop is constructed by graphing Flow on the y-axis and time on the x-axis. The diagnosis of Asthma is made when the FEV1/FVC is blow 75% and there is a 15% improvement in the FEF25-75 after bronchodilator therapy. If the downward portion of the curve is concave (non linear) then this suggests airway obstruction. In other words, flow that drops rapidly at first, then diminishes slowly over time is diagnostic for trapping of airflow. A typical Flow Volume loop and tale appears as follows:

Figure 2, Flow Volume Loop

Figure 2

Flow is expressed as the (change in volume)/time on the y-axis measured against volume on the x-axis. Normal flow shows a linear relationship. Obstruction shows a bend that we call concave downward. Red shows the state before a bronchodilator is administered, and the green shows flow after a bronchodilator. In this case, there is an improvement.

Table 2, Pulmonary Function Test Example

ParameterSpirometryResult(L)Predicted(%)Result(L)Predicted(%)Change(%)
FEV13.55814.64106+30
FVC5.18996.06116+16
FEV1/FVC68817791+11
FEF25-752.41503.8480+59

In the above example, the FEV1/FVC under 75% and the FEF25-75 improvement of 59% indicates both air trapping and a marked improvement after a brochodilator treatment. The concavity of the curve and the near linearity after treatment supports the diagnosis.

Asthma is classified into one of four groups: Intermittent, Mile Persistent, Moderat Persistent or Severe Persistent.[2] Current consensus is based on the baseline symptoms at time of diagnosis and the intensity of treatment required to achieve good control.

Treatment of Asthma

The Global Initiative for Asthma (GINA) is a guideline used for the treatment of Asthma.[2]

The GINA guideline is comprehensive and does not include an easy to follow algorithm. In lieu of this, I will give my personal approach to Asthma. I use a stepwise approach to control symptoms. First, I initiate a short acting beta agonist (SABA). The most cost effective drug is albuterol (ProAir) as a hand held device. It is given as a puff separated by two minutes administered every four hours as needed. Often this is referred to as a rescue inhaler. Examples of SABA are listed in the table below.

If SABA do not control symptoms, the next step in Asthma is to add an ICS. Most physicians will use a combination inhaler such as Advair or Symbicort. There is recent literature that challenges this approach in theat a SABA taken with a LABA may be sufficient as a next step.

If hand held inhalers are not sufficient, then nebulized solutions are often used. Duoneb via nebulizer every 4-6 hours as needed is a common medication combination.

If ICS are not sufficient for controlling symptoms, the next step is to add oral corticosteroids such as prednisone. Exacerbations are often treated with a pulse of oral steroids such as a step down approach, such as initiating with 40 mg orally per day for 3 days, dropping to 30 mg per day for 3 days, dropping to 20 mg per day for 3 days, dropping to 10 mg per day for 3 days, then off. Another approach is to give 40 mg orally per day for 5 days, then off.[3] Oral steroids are met with a long list of complications which is why ICS are preferred.

The GINA uses the following table as a step-wise approach:

Table 3, GINA Step-wise Therapy for Asthma

Step 1Step 2Step 3Step 4Step 5
SABAICSICS + LABAICS + LABAPrednisone
Leuk IICS-highLeuk IAnti-IgE
ICS + Leuk ITheo
ICS + Theo

Anti-IgE= Anti-Immunoglobulin E; ICS= Inhaled CorticoSteroid; LABA= Long Acting Beta Agonist; Leuk= Leukotriene Inhibitor; SABA= Short Acting Beta Agonist; Theo= Theophylline

Treatment of COPD

The Global Initiative for Obstructive Lung Disease (GOLD), is a guideline used for the treatment of Chronic Obstructive Pulmonary Disease (COPD).[3]

The GOLD guideline takes a Dyspnea Scale and an FEV1 Score, and combines them into a Classification scheme: A, B, C, D. Class A is mild disease and Class D is severe disease.

Table 4, Gold Classification

4
3
CD
2
1
AB
0-12

where the y-axis is defined by FEV1 with a mid cutoff of FEV1<50% and the x-axis is defined by mMRC with a mid cutoff of symptoms with mild exertion. (Refer to the next two tables)

Table 5, Modified Medical Research Council (mMRC) Dyspnea Scale

ScaleSymptom
0No sx
1No SOB but has DOE with strenuous exercise
2SOB when in a hurry on level ground or walking up a slight hill
3Walk slower than most people on level ground, stops
after a mile, stops after 15 minutes while walking a normal pace
4Stops to catch a breath after walking ~100 yards or after a few minutes
on level ground
5SOB after dressing or too SOB to leave the house

Table 6, FEV1 Score

ScoreLevelValue
4Very severeFEV1 < 30%
3SevereFEV1 30-50%
2ModerateFEV1 50-80%
1MildFEV1 > 80%

Based on the above GOLD Classification, this will help guide therapy by the following table:

Table 7, Treatment for COPD According to GOLD Groups

GroupFirstSecondAlternate
ASABA prn or
SAMA prn
LAMA or
LABA or
SABA + SAMA
Theophylline
BLABA or
LAMA
LABA + LAMASABA +/- SAMA or
SAMA
CICS + LABA or
LAMA
LABA + LAMAPDE-4-I or
SABA +/- SAMA or
Theophylline
DICS + LABA or
LAMA
ICS + LAMA or
ICS + LABA + LAMA or
ICS + LABA + PDE4-I or
LABA + LAMA or
LAMA + PDE-4-I
Carbocysteine or
SABA +/- SAMA or
Theophylline

Abbreviations SABA short acting beta agonist such as albuterol; SAMA Short-acting muscarinic antagonist such as Ipratropium; LABA long acting beta agonist such as salmeterol; LAMA Long Acting Muscarinic Antagonist such as tiotropium; ICS inhaled corticosteroid such as Fluticasone; PDE-4-I phosphodiesterase-4 inhibitor such as Theophylline.

Traditionally, in COPD, in the GOLD Class C patients, usually physicians will advance to an inhaled corticosteroid (ICS) plus Long Acting Beta Agonist (LABA) or a Long Acting Muscarinic Antagonist (LAMA).[7] Now there is a study that supports the use of a LABA-LAMA combination.[8] The use of Stiolto may now be used and avoid some of the Adverse Drug Events (ADEs) which may occur with inhaled corticosteroids (ICS).

Table 8. Bronchodilators

Short Acting Beta Agonist (SABA)

Generic(Brand)DoseInstructionsPrice($)
Albuterol (ProAir)90 mcg/sprii puffs q4h prn62
Albuterol (Ventolin)90 mcg/sprii puffs q4h prn74
Albuterol2.5 mg/3ml3 ml q4h prn12
Levalbuterol (Xopenex)45 mcg/sprii puffs q4h prn34
Levalbuterol (Xopenex)1.25 mg/3ml3ml q4h prn513

Short Acting Muscarinic Antagonist (SAMA)

Generic(Brand)DoseInstructionsPrice($)
Ipratropium (Atrovent)17 mcg/sprii puffs qid301
Ipratropium0.5 mg/2.5ml2.5 ml qid prn27
Ipra-Albu (Duoneb)0.5mg/2.5mg/3ml3ml q4h prn372

Long Acting Beta Agonist (LABA)

Generic(Brand)DoseInstructionsPrice($)
Arformoterol (Brovana)15 mcg/2ml2ml q12h874
Formoterol (Performist)20 mcg/2ml2ml q12h870
Salmeterol (Serevent)50 mcg/actI puff q12h56
Olodaterol (Striverdi)2.5 mcg/actii puffs qd180

Long Acting Muscarinic Antagonist (LAMA)

Generic(Brand)DoseInstructionsPrice($)
Tiotropium (Spiriva)18 mcg/capI inh qd385
Tiotropium (Spiriva)2.5 mcg/actii puffs qd368
Umeclidinium (Incruse)62.5 mcg/actI puff qd288
Aclidinium (Tudorza)400 mcg/actI puff bid363

Inhaled Corticosteroid (ICS)

Generic(Brand)DoseInstructionsPrice($)
Budesonide (Pulmicort)180 mcg/actii puffs bid254
Budesonide (Pulmicort)0.5 mg/2ml2ml q6h536
Fluticasone (Flovent)250 mcg/acti puffs bid254
Fluticasone (Flovent)110 mcg/actii puffs bid78
Budes-form (Symbicort)160 mcg/4.5 mcgii puffs bid340
Flutic-salm (Advair)250 mcg/50mcgI inh bid366
Flutic-salm (Advair)115 mcg/21mcg2 puffs q12h408
Flutic-vilan (Breo)100 mcg/25mcgI puff qd360
Momet-form (Dulera)200 mcg/5mcg/spr2 puffs bid308

LABA-LAMA Combinations

Generic(Brand)DoseInstructionsPrice($)
olodat-tiotrop (Stiolto)2.5 mcg/2.5mcg/actii puffs qd320

Leukotriene Inhibitor

Generic(Brand)DoseInstructionsPrice($)
Montelukast (Singulair)10 mgI po qd197
Zafirlukast (Accolate)20 mgI po bid182
Zileuton (Zyflo)600 mgI po qid3512

Theophylline

Generic(Brand)DoseInstructionsPrice($)
Theo-24300 mgI po qd96
Uniphyl400 mgI po qd30
Elixophyllin80 mg/15ml15 ml q6h260

Anti-IgE Therapy

Generic(Brand)DoseInstructionsPrice($)
Omalizumab (Zolair)150 mgsc q2wk2,098
Mepolizumab (Nucala)100 mgsc q4wk2,708

Note: prices are monthly estimates in US dollars

Reference

  1. Postma, Dirkje S, et al, The Asthma-COPD Overlap Syndrome, New England Journal of Medicine, 2015; vol 373: pp 1241-1249. click here
  2. Global Initiative for Asthma, Global Strategy for Asthma Management and Prevention, Updated 2010, www.ginasthma.org
  3. Leuppi JD, Schuetz P, Binssinger R, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013; vol 309: pp 2223-2231. click here
  4. Martinez, FD, Safety of Fluticasone plus Salmeterol in Asthma--Reassuring Data, but No Final Answer, New England Journal of Medicine, 2016, vol 374, pp 1887-1888. click here
  5. Stempel DA, et al, Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone, New England Journal of Medicine, 2016, vol 374: pp 1822-1830. click here
  6. 6. Global Initiative for Obstructive Lung Disease, Pocket Guide to COPD Diagnosis, Management, and Prevention, A Guide for Health Care Professionals, Revised 2011. click here
  7. 7. Tashkin DP, et al, A 4-Year Trial of Tiotropium in Chronic Obstructive Pulmonary Disease, New England Journal of Medicine, 2008, vol 359: pp 1543-1554. click here
  8. 8. Wedzicha, JA, et al, Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD, New England Journal of Medicine, 2016, vol 374: pp 2222-2234. click here

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