Focus on Asthma and COPD
A Peer-Reviewed Newsletter – Issue 3
April 2011

The Importance of Accurate Obstructive Respiratory Disease Diagnoses: A Comparison of Asthma and Chronic Obstructive Pulmonary Disease

Gabriel Ortiz

Gabriel Ortiz

MPAS, PA-C, DFAAPA
Pediatric Pulmonary Services,
El Paso, Texas

Gabriel Ortiz serves as the American Academy of Physician Assistants (AAPA) liaison to the American Academy of Allergy, Asthma & Immunology (AAAAI) and as the AAAAI liaison to the AAPA.

He has served previously as the AAPA liaison to the National Asthma Education and Prevention Program.

Consultant: Merck, Sunovion, TEVA
Speakers Bureau: Merck, Phadia Diagnostics Inc, TEVA

Other articles by the same author in this e-newsletter series:

Summary Information for Inhaled Corticosteroid and Long-Acting β2-Adrenergic Agonist Combination Product Use in Patients in the United States Who Have Asthma or Chronic Obstructive Pulmonary Disease.

Available at: http://www.advanceweb.com/web/
focus_on_asthma_copd/article1.html

Applying the 2009 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines for the Pharmacological Management of Chronic Obstructive Pulmonary Disease in Clinical Practice.

Available at: http://www.advanceweb.com/web/
astrazeneca/copd/gold_guidelines.html

Key Points

  • Both asthma and chronic obstructive pulmonary disease (COPD) are obstructive respiratory disorders characterized by airflow limitation and inflammation. However, the pathogenesis of each disease is distinct, and each disease has distinguishing characteristics.
  • Establishing a diagnosis of asthma, COPD, or both may be challenging because of overlapping disease characteristics and the possibility for both diseases to coexist; however, an accurate diagnosis is necessary because disease management strategies and treatment approaches are different for each disease.
  • The following approaches may help to distinguish between asthma and COPD.
  • Assess the patient’s history and identify key disease indicators and demographic, clinical, and pathophysiological features.
  • Use spirometry to characterize pulmonary function
  • Use questionnaires in patients with suspected asthma or COPD
  • Exclude alternative diagnoses
  • Once diagnosed, disease severity (or level of asthma control for patients already receiving treatment) should be determined and corresponding treatments should be prescribed according to current guideline recommendations (eg, National Asthma Education and Prevention Program [NAEPP] guidelines for asthma; Global initiative for chronic Obstructive Lung Disease [GOLD] guidelines for COPD).
Case Study

M.T. is 48 years old and a new patient at his clinician’s practice. He was previously diagnosed with moderate persistent asthma and is being treated accordingly. He presents with symptoms of chronic cough and shortness of breath. In addition, M.T. notes that he does not feel that his current medication is working. Upon evaluation, he reveals a previous 20–pack-year smoking history, although he quit several years ago. Due to these factors, his clinician suspects that M.T. may have developed COPD in addition to asthma or may have been misdiagnosed previously.

Overview of Asthma and COPD

Both asthma and COPD are obstructive respiratory disorders that are characterized by inflammation and airway limitation and associated with varying degrees of severity [1, 2]. In 2008, the estimated prevalence in the United States was 23 million for asthma and 12 million for COPD [3, 4]. Although both diseases share common characteristics, each is associated with distinct pathophysiological mechanisms mediated by specific cell types and factors (Figure 1) [1-5]; therefore, each disease has distinguishing features. Asthma is characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and underlying inflammation [1]. Recurrent airflow limitation may be caused by bronchoconstriction, airway edema, airway hyperresponsiveness, or airway remodeling [1]. COPD is characterized by chronic and progressive airflow limitation that is not fully reversible, resulting from a combination of inflammatory small airway disease (obstructive bronchiolitis) and parenchymal destruction (emphysema) [2]. COPD also is associated with significant pathological lung changes, extrapulmonary effects, and comorbidities [2]. Each disease also has predisposing risk factors, most commonly atopy for asthma [1] and smoking for COPD [2]. Lung inflammation in severe asthma and COPD may be similar [2]; however, distinct attributes of these diseases can be used to distinguish between them. Because disease management strategies and treatment approaches are different for asthma and COPD [1, 2], an accurate diagnosis should be established as early as possible to avoid potential adverse outcomes and health care costs associated with inappropriate disease management. This newsletter reviews characteristic features, diagnostic tools, and management approaches for asthma and COPD.

Figure 1. Pathologic Changes and Inflammatory Mediators in Asthma and COPD

Figure 1

BSM, bronchial smooth muscle; CD, cluster of differentiation; COPD, chronic obstructive pulmonary disease; IL, interleukin; LTB4, leukotriene B4; Th, T helper; TNF-α, tumor necrosis factor-α.

Source: Doherty DE. The pathophysiology of airway dysfunction. Am J Med. 2004;117(12A):11S-23S [5].

Considerations for Diagnosis

Characteristic Features

Early recognition of suggestive symptoms may help clinicians establish diagnoses of chronic respiratory diseases [6]. Symptoms common to many types of airway disease include cough; wheeze; breathlessness; shortness of breath; chest tightness; nose that is runny, blocked, or itchy; and limitation of usual activities [6]. Establishment of a firm diagnosis of asthma or COPD may be particularly challenging because of overlapping disease characteristics [7]. Identification of key indicators (Table 1) may help to distinguish asthma or COPD from other respiratory diseases and from each other [1, 2]. Notably, dyspnea/difficulty breathing and cough are indicators of both diseases; however, a chronic cough may suggest COPD while a history of coughing that worsens particularly at night may be indicative of asthma [1, 2].

Table 1. Considerations for Diagnosis of Asthma and COPD

aLack of wheezing and normal examination do not exclude asthma as a diagnosis; bparticularly when worse at night; cincludes animals with fur or hair, house-dust mites, mold, smoke, pollen, airborne chemicals or dusts.

COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity.

Differences between asthma and COPD also exist in the types of infiltrating cells and inflammatory markers present, age at onset, persistency of symptoms, exercise capacity, and smoking history [1, 2]. Although eosinophils are the predominant effector cell, other prominent infiltrating cells and inflammatory markers during asthma pathogenesis include neutrophils, lymphocytes, activated mast cells, injured epithelial cells, interleukin-5 (IL-5), IL-4, IL-13, immunoglobulin E, and nitric oxide [1]. Onset of asthma and persistence most commonly occur early in life [1], with rates of asthma prevalence higher in children than in adults [11]. Symptoms of asthma are often variable and may be aggravated by environmental allergens, viral respiratory infections, and other irritants [1]. Exercise also may trigger or worsen symptoms of asthma [1].

Hallmarks of COPD inflammation include neutrophil, macrophage, and lymphocyte infiltration with mediation by leukotriene B4, IL-8, transforming growth factor-β, and proinflammatory cytokines (eg, tumor necrosis factor-α) [2]. COPD often develops during middle age [2]; current prevalence rates are highest among adults at least 45 years old [4]. Although considered a disease that primarily affects men, current data suggest almost equal prevalence rates between genders, possibly reflecting the increased rate of smoking among women [2]. COPD is associated with chronic symptoms and risk of continual lung function decline [2, 8]. Reduced exercise capacity is often apparent at moderate and severe stages of disease and is a result of airway hyperinflation [2]. A history of smoking, combined with specific respiratory symptoms (described above), suggests COPD since most cases occur in long-time smokers [2, 9].

Coexisting Asthma and COPD

Asthma and COPD have many overlapping features [12], and distinguishing between the 2 diseases may be more difficult in the elderly and in patients with a long history of asthma [2, 12]. Data from the US National Health and Nutrition Examination III survey indicate that a substantial number of patients in the United States are diagnosed with both asthma and COPD (chronic bronchitis or emphysema) [13]. In patients with coexisting chronic asthma and COPD, the GOLD guidelines suggest disease management according to the asthma component [2].

Diagnostic Tools

Spirometry: The diagnosis of asthma is determined in part by the presence of airway hyperresponsiveness or episodic symptoms of airflow obstruction that is at least partially reversible [1]. Spirometry, which measures forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and other lung function parameters, is used to demonstrate airflow obstruction and assess reversibility [1]. Increases in FEV1 and/or FVC ≥ 200 mL and ≥ 12% above prebronchodilator levels have been suggested to represent significant bronchodilator reversibility by a joint task force of the American Thoracic Society and European Respiratory Society [10, 14]. Other methods for establishing an asthma diagnosis include a detailed medical history; a physical examination focused on the upper respiratory tract, chest, and skin; and additional studies to exclude alternative diagnoses [1].

Spirometry also is recommended to make a confident diagnosis of COPD through measurement of airflow limitation and should be undertaken in all patients who may have COPD [2]. In particular, spirometry is required to establish an accurate diagnosis in patients with symptoms, risk factors, or suspicion of COPD [15]. COPD is characterized by airflow limitation that is not fully reversible [2], defined as the presence of a postbronchodilator FEV1/FVC < 0.70; disease severity is ascribed according to postbronchodilator FEV1 percent of predicted normal [2]. The extent to which airflow obstruction is reversible in patients with COPD has not been determined definitively; however, several clinical studies have reported significant bronchodilator responsiveness in a substantial proportion of patients with COPD [16-19]. Degree of airflow limitation is no longer recommended for determination of a COPD diagnosis [2].

Table 2. Four-Item Questionnaire for Differentiating Asthma and COPD

aScores range from 0–15 points. High scores indicate COPD while low scores suggest asthma.

COPD, chronic obstructive pulmonary disease.

Source: Beeh KM, Kornmann O, Beier J, Ksoll M, Buhl R. Clinical application of a simple questionnaire for the differentiation of asthma and chronic obstructive pulmonary disease. Respir Med. 2004;989(7):591-597 [21].

Questionnaires: Symptom-based questionnaires may be useful for improving the diagnostic accuracy of obstructive lung diseases when used together with spirometry [20]. Beeh et al designed and validated a simple, 4-item questionnaire to assist health care providers in distinguishing between asthma and COPD (Table 2) [21]. Total scores range from 0 to 15; high and low scores support diagnoses of COPD and asthma, respectively [21]. Scores of 6 to 8 indicate obstructive disease that cannot be distinguished easily. During the study, patients with scores of 6 to 8 included COPD patients with atopy and greater bronchodilator reversibility and nonallergic patients with asthma who smoked more heavily [21]. A validated 9-item differential diagnosis questionnaire showed utility in identifying patients likely to have COPD in a population of patients at least 40 years old with previous evidence of obstructive lung disease [20, 22]. This questionnaire included items evaluating the patient’s age (1 item), smoking intensity
(1 item), and respiratory symptoms (7 items)
[22]. Screening questionnaires specific to
COPD [23-24] and asthma control [25] also
are available.

Case Study Continued

The clinician recognizes that M.T.’s chronic cough and dyspnea may be key indicators of COPD. Upon further evaluation, M.T. notes that his tolerance for exercise has decreased in the past 2 years despite treatment for asthma. In addition, M.T. scores a 12 on a questionnaire (scale of 0 to 15, with higher scores indicating COPD and lower scores indicating asthma). Spirometry results included an FEV1/FVC ratio of 0.62 after albuterol administration. Combined with M.T.’s history of smoking and lack of asthma as a child, his clinician diagnoses M.T. with COPD.

Alternative Diagnoses

Alternative diagnoses also should be considered during patient evaluation for COPD or asthma (Figure 2) [1, 2]. These alternative diagnoses are generally distinct for asthma and COPD; however, congestive heart failure may be considered in the differential diagnosis for both COPD and asthma [1, 2]. Suggestive features for alternative diagnoses for COPD were reviewed in a previous article in this series. (View Mr. Ortiz’s e-newsletter on the GOLD guidelines) Differential diagnosis may be based on results of routine evaluation (medical history, physical examination, and pulmonary function testing) or additional studies if needed (additional pulmonary function testing [lung volume, inspiratory flow-volume loops, diffusing capacity], bronchoprovocation when spirometry results are normal or near normal, chest X ray, computed tomography, allergy testing, or measurement of inflammatory biomarkers [1, 2].

Figure 2. Differential Diagnostic Possibilities for COPD and Asthma in Adults

Figure 2

aIncluding benign and malignant tumors; beg, angiotensin-converting enzyme inhibitors.

Sources: the National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma—Full Report 2007. NIH Publication Number 08-4051, 2007 [1] and the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD). Updated 2010. Available at: http://www.goldcopd.org [2].

Assessment of Disease Severity and Recommended Treatments

Once a diagnosis of asthma, COPD, or both has been made, disease severity should be determined to establish appropriate therapy (Figure 3, Table 3) [1, 2]. For patients diagnosed with asthma who are already receiving treatment, the level of control should be assessed for adjustments to therapy (Figure 4) [1]. For adolescents (at least 12 years old) and adults diagnosed with asthma, levels of severity and asthma control are assessed based on measures of impairment and risk (Figures 3 and 4) [1]. Patient recall of increased impairment (asthma symptoms, nighttime awakenings, short-acting β2-adrenergic use, and interference with normal activity) within 2–4 weeks, decreased lung function as measured by spirometry (or peak flow when assessing asthma control), and increased frequency and intensity of exacerbations imply greater disease severity or worse asthma control [1]. Worse scores on validated asthma control questionnaires also indicate worse asthma control [1]. The level of severity or asthma control should be assigned according to the most severe category in which any impairment or risk feature occurs [1]. Treatment algorithms for asthma based on disease severity and level of control are cited in the National Asthma Education and Prevention Program guidelines [1] and previously reviewed. (View Mr. Ortiz’s e-newsletter on combination long-acting β2-adrenergic product use) Appropriate treatment based on COPD severity, according to the GOLD guidelines, has been reviewed in the second article in this series. (View Mr. Ortiz’s e-newsletter on the GOLD guidelines)

Figure 3. Severity Classification in Patients With Asthma Who Have Not Initiated Treatment

Figure 3

Notes:

  • The stepwise approach is meant to assist, not replace, the clinical decision making required to meet individual patient needs.
  • Level of severity is determined by assessment of both impairment and risk. Assess impairment domain by patient’s/caregiver’s recall of previous 2–4 weeks and spirometry. Assign severity to the most severe category in which any feature occurs.
  • At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma severity. In general, more frequent and intense exacerbations (eg, requiring urgent, unscheduled care, hospitalization, or intensive care unit admission) indicate greater underlying disease severity. For treatment purposes, patients who had at least 2 exacerbations requiring oral systemic corticosteroids in the past year may be considered the same as patients who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma.

EIB, exercise-induced bronchoconstriction; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity.

Source: the National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma—Full Report 2007. NIH Publication Number 08-4051, 2007 [1].

__________________________________

Figure 4. Asthma Control Classification in Patients With Asthma Who Have Initiated Treatment

Figure 4

aACQ values of 0.76−1.4 are indeterminate regarding well-controlled asthma.

Notes:

  • The stepwise approach is meant to assist, not replace, the clinical decision making required to meet individual patient needs.
  • The level of control is based on the most severe impairment or risk category. Assess impairment domain by patient’s recall of previous 2–4 weeks and by spirometry or peak flow measures. Symptom assessment for longer periods should reflect a global assessment, such as inquiring whether the patient’s asthma is better or worse since the last visit.

  • At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma control. In general, more frequent and intense exacerbations (eg, requiring urgent, unscheduled care, hospitalization, or intensive care unit admission) indicate poorer disease control. For treatment purposes, patients who had at least 2 exacerbations requiring oral systemic corticosteroids in the past year may be considered the same as patients who have not-well-controlled asthma, even in the absence of impairment levels consistent with not-well-controlled asthma.
  • Validated questionnaires for the impairment domain (the questionnaires do not assess lung function or the risk domain)
    • Minimal important difference: 1.0 for the ATAQ; 0.5 for the ACQ; not determined for the ACT
  • Before step up in therapy:
    • Review adherence to medication, inhaler technique, environmental control, and comorbid conditions.
    • If an alternate treatment option was used in a step, discontinue and use the preferred treatment for that step.

ACQ, Asthma Control Questionnaire; ACT, Asthma Control Test; ATAQ, Asthma Therapy Assessment Questionnaire; EIB, exercise-induced bronchoconstriction; FEV1, forced expiratory volume in 1 second; N/A, not applicable.

Source: the National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma—Full Report 2007. NIH Publication Number 08-4051, 2007 [1].

_____________________________________

Table 3. Spirometric Classification of COPD Severity Based on Postbronchodilator FEV1

aArterial partial pressure of oxygen <#8.0 kPa (60 mmHg) with or without partial pressure of CO2 > 6.7 kPa (50 mmHg) while breathing air at sea level.

COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity.

Content from the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD). Updated 2010. Used with permission from the Global Initiative for Chronic Obstructive Lung Disease [2].

Goals for treatment of COPD include prevention and control of symptoms, reduction of the frequency and severity of exacerbations, and improvement of health status and exercise tolerance [2]. A goal of asthma therapy for patients 12 years and older is to maintain control of asthma, defined as reduction of impairment and risk, with the least amount of medication and minimal risk for adverse events [1]. Assessment of patient inhaler technique is recommended as part of regular follow-up for adults with asthma and COPD [1, 2]. Patients may also benefit from supplemental instruction on inhaler technique by community-based pharmacists [26].

Additional spirometry results reveal M.T. to have a postbronchodilator FEV1 of 64% (and an FEV1/FVC ratio of 0.62, as above), indicating COPD of moderate severity. Based on these and supporting findings, M.T.’s health care provider will prescribe a treatment regimen according to GOLD guidelines for stage II COPD, including regular maintenance therapy with at least 1 bronchodilator (eg, tiotropium, formoterol, salmeterol) and pulmonary rehabilitation. The addition of an inhaled corticosteroid to long-acting inhaled bronchodilator therapy is recommended in patients with GOLD stage III (severe) or IV (very severe) COPD with a history of repeated exacerbations [2].

Summary

Overlapping features of asthma and COPD may make confident diagnosis of either disease challenging for clinicians. Airway inflammation in particular is a critical component of both asthma and COPD. However, these diseases have distinct pathogenic mechanisms and require different strategies for appropriate management. Therefore, it is critically important that clinicians make an accurate diagnosis of asthma, COPD, or both upon patient presentation with symptoms. Spirometry, supported by other screening and diagnostic tools, is strongly recommended for differentiation between these obstructive respiratory diseases in clinical practice.

Acknowledgements

The author thanks Kristen Quinn, PhD, and Cynthia Gobbel, PhD, from Scientific Connexions (Newtown, PA), who provided medical writing support funded by AstraZeneca LP (Wilmington, DE).

References

  1. National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma—Full Report 2007. NIH Publication Number 08-4051, 2007.
  2. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Updated 2010. Available at: http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=989. Accessed April 12, 2011.
  3. American Lung Association. Trends in Asthma: Morbidity and Mortality. 2010. http://www.lungusa.org/finding-cures/our-research/trend-reports/asthma-trend-report.pdf. Accessed January 11, 2011.
  4. American Lung Association. Trends in COPD (Chronic Bronchitis and Emphysema): Morbidity and Mortality. 2010. http://www.lungusa.org/finding-cures/our-research/trend-reports/copd-trend-report.pdf. Accessed January 12, 2011.
  5. Doherty DE. The pathophysiology of airway dysfunction. Am J Med. 2004;117(12A):11S-23S.
  6. Levy ML, Fletcher M, Price DB, Hausen T, Halbert RJ, Yawn BP. International primary care respiratory group (IPCRG) guidelines: diagnosis of respiratory diseases in primary care. Prim Care Respir J. 2006;15(1):20-34.
  7. Dima E, Rovina N, Gerassimou C, Roussos C, Gratziou C. Pulmonary function tests, sputum induction, and bronchial provocation tests: diagnostic tools in the challenge of distinguishing asthma and COPD phenotypes in clinical practice. Int J Chron Obstruct Pulmon Dis. 2010;5:287-296.
  8. Celli BR. The importance of spirometry in COPD and asthma: effect on approach to management. Chest. 2000;117(2 suppl):15S-19S.
  9. Sutherland ER, Martin RJ. Airway inflammation in chronic obstructive pulmonary disease: comparisons with asthma. In: Nelson HS, series ed. Current reviews of allergy and clinical immunology. J Allergy Clin Immunol. 2003;112(5):819-827.
  10. Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. In: Brusasco V, Crapo R, Viegi G, series eds. ATS/ERS Task Force: standardisation of lung function testing. Number 5 in the series. Eur Respir J. 2005;26(5):948-968.
  11. Moorman JE, Rudd RA, Johnson CA, et al. National surveillance for asthma—United States, 1980–2004. MMWR Surveill Summ. 2007;56(SS-8):1-54.
  12. Diaz-Guzman E, Mannino DM. Airway obstructive diseases in older adults: from detection to treatment. J Allergy Clin Immunol. 2010;126(4):702-709.
  13. Soriano JB, Davis KJ, Coleman B, Visick G, Mannino D, Pride NB. The proportional venn diagram of obstructive lung disease: two approximations from the United States and the United Kingdom. Chest. 2003;124(2):474-481.
  14. American Thoracic Society. Lung function testing: selection of reference values and interpretative strategies. Am Rev Respir Dis. 1991;144(5):1202-1218.
  15. Fromer L, Barnes T, Garvey C, Ortiz G, Saver DF, Yawn B. Innovations to achieve excellence in COPD diagnosis and treatment in primary care. Postgrad Med. 2010;122(5):150-164.
  16. Calverley PMA, Burge PS, Spencer S, Anderson JA, Jones PW; for the ISOLDE Study Investigators. Bronchodilator reversibility testing in chronic obstructive pulmonary disease. Thorax. 2003;58(8):659-664.
  17. Bleecker ER, Emmett A, Crater G, Knobil K, Kalberg C. Lung function and symptom improvement with fluticasone propionate/salmeterol and ipratropium bromide/albuterol in COPD: response by beta-agonist reversibility. Pulm Pharmacol Ther. 2008;21(4):682-688.
  18. Tashkin DP, Celli B, Decramer M, et al. Bronchodilator responsiveness in patients with COPD. Eur Respir J. 2008;31(4):742-750.
  19. Celli BR, Tashkin DP, Rennard SI, McElhattan J, Martin UJ. Bronchodilator responsiveness and onset of effect with budesonide/formoterol pMDI in patients with COPD. Respir Med. 2011. In press.
  20. Tinkelman DG, Price DB, Nordyke RJ, et al. Symptom-based questionnaire for differentiating COPD and asthma. Respiration. 2006;73(3):296-305.
  21. Beeh KM, Kornmann O, Beier J, Ksoll M, Buhl R. Clinical application of a simple questionnaire for the differentiation of asthma and chronic obstructive pulmonary disease. Respir Med. 2004;989(7):591-597.
  22. Price DB, Tinkelman DG, Nordyke RJ, Isonaka S, Halbert RJ. Scoring system and clinical application of COPD diagnostic questionnaires. Chest. 2006;129(6):1531-1539.
  23. Martinez FJ, Raczek AE, Seifer FD, et al; on behalf of the COPD-PS Clinician Working Group. Development and initial validation of a self-scored COPD population screener questionnaire (COPD-PS). COPD. 2008;5(2):85-95.
  24. Yawn BP, Mapel DW, Mannino DM, et al; on behalf of the Lung Function Questionnaire Working Group. Development of the lung function questionnaire (LFQ) to identify airflow obstruction. Int J COPD. 2010;5:1-10.
  25. Nathan RA, Sorkness CA, Kosinski M, et al. Development of the Asthma Control Test: a survey for assessing asthma control. J Allergy Clin Immunol. 2004;113(1):59-65.
  26. Hämmerlein A, Müller U, Schulz M. Pharmacist-led intervention study to improve inhalation technique in asthma and COPD patients. J Eval Clin Pract. 2011;17(1):61-70.