Adherence to Prescribed Medication and Its Association with Quality of Life Among COPD Patients Treated at a Tertiary Care Hospital in Puducherry – A Cross Sectional Study

S Keerti kumar S

B Maharani, MD

R Venkateswara Babu, MD

M Prakash, MD 

Departments of Pharmacology, Respiratory Medicine and Community Medicine

Indira Gandhi Medical College and Research Institute

Puducherry, India

Abstract

Introduction: Medication adherence is a major determinant for the success of therapy among chronic obstructive pulmonary disease (COPD) patients. The research objectives of the present study were to assess the adherence to prescribed medications and its association with quality of life among COPD patients, to determine the major factors that influence the medication adherence and to assess patient’s knowledge on COPD and its relation to medication adherence.

Methods: It was a hospital based cross-sectional study. Patient demographic characteristics, smoking and alcoholic status, severity grading of COPD, concomitant disease, affordability of patients to medication, patient knowledge on COPD (Knowledge Questionnaire), adherence to medication and inhaler, major factors influencing adherence, disease control and quality of life (COPD Assessment Test) were recorded.

Results: Most of the patients were non-smokers and patients exposed to occupational air pollutants was high. Complete adherence to prescribed medication was found among 47% (MAS Score 6) of the participants and 81% of the participants were partially adherent (MAS score, range of 1-6). Highly adherent group was found to have high CAT score which was statistically significant. (P=0.020). Major factors for medication non-adherence were forgetfulness (82.5%) and symptomatic relief of illness (12.5%). There was no statistically significant association between individual knowledge questions and medication adherence except the question “COPD medicines prevent the disease from getting worse” (P=0.021).

Conclusion: There was a statistically significant association between medication adherence and quality of life. Appropriate health education should be implemented for improving patient awareness and medication adherence.

Introduction

Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases (1). In industrialized and developed countries, it is one of the leading causes of morbidity and mortality (2). The World Health Organization predicts that COPD will become the third leading cause of death by 2030 (3). Currently, various drugs like β2 agonist (long and short acting), inhalational anticholinergics, inhalational corticosteroids and methyl xanthines are utilized to prevent, control the symptoms and also to minimize the occurrence of COPD exacerbations (4,5).

The main factor that determines the success of therapy appears to be medication adherence. The medication adherence rates among COPD patients in clinical trials has been found to be 70 to 90% but in clinical practice it was very low accounting for only 10 to 40% (6-11). Non-adherence to therapy may lead to poor health and increased morbidity and health care cost, which in turn alters the quality of life (12). There appear to be few studies in India on medication adherence among COPD patients. This study is novel in assessing the adherence to drug therapy and its relation to quality of life, patients’ knowledge on COPD and its relationship to medication adherence and major factors influencing the medication adherence among COPD patients attending the tertiary care Institute in one of the Union Territory in India. 

Methods

Study design and setting: A cross-sectional study was conducted in a tertiary care hospital. The study center was a referral hospital for nearby primary and secondary care hospitals and a separate COPD clinic was run every week for treating COPD patients. The study was conducted for a period of 6 months after obtaining Institutional Ethics Committee clearance.

Study Population: Eligible patients were those referred and diagnosed with COPD by FEV1 and categorized according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging and were receiving medications (with no alterations in treatment regimen during the past 3 months). Since the study was on medication adherence, all the COPD patients attending the outpatient department during the study period were considered. Patients with a history of asthma, allergic rhinitis, hospitalization for COPD exacerbation in last 3 months, heart failure or serious liver disease or renal failure or acute coronary syndrome patients and mental illness patients were excluded.

Data Collection: The patients satisfying the inclusion criteria were interviewed after obtaining their written informed consent. Patient demographic details, smoking and alcoholic status, occupational exposure to air pollutants, age at diagnosis of COPD, duration of COPD, concomitant disease, affordability of patients to medication were recorded. Post-bronchodilator FEV1 was measured with spirometry and grading of COPD was done following Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging (13).  

Questionnaires used: Patient knowledge on COPD was assessed using COPD Knowledge Questionnaire (COPD-Q) (14). It is a valid, reliable and low-literacy tool to assess COPD related knowledge in patients. Adherence to medication and inhaler was evaluated by using Medication Adherence Scale (MAS) and Medication adherence report scale (MARS) (15,16). Reasons for non-adherence (missing or discontinuing the dose) were also obtained from the patients.  Disease control and quality of life was assessed by using COPD assessment Test (CAT) (17). CAT score varies with changes in treatment and exacerbations of disease due to poor adherence. CAT scoring ranges between 0 and 40. Score of

> 30                - very high impact of COPD on patients

>20                 - high impact of COPD on patients

10 to 20         - medium impact of COPD on patients

<10                - low impact of COPD on patients

5                   - very low impact of COPD on patients

Statistical Analysis: Data entry was done in MS Excel 2010.  Data was analyzed using professional statistics package EPI Info 7.0 version for windows. Descriptive data was represented as mean ± SD, median and interquartile range for numeric variables, percentages and proportions for categorical variables. Appropriate tests of significance were used depending on nature & distribution of variables like Chi square test, student’s t test for categorical variables. Values of p<0.05 were considered statistically significant. Spearman’s correlation test was used to find out the relationship between medication adherence and quality of life.

Results

During the six months study period, 157 COPD patients were contacted. Out of the 157 patients, 19 patients refused to participate in the study, 5 patients were not able to answer appropriately and 42 patients had not satisfied the inclusion criteria. A total of 91 patients completed the study and gave complete responses to the questionnaire. 

Sociodemographic characteristics of the patients were summarized in Table 1.

Table 1. Sociodemographic characteristics of the study participants.

Most of the patients were non-smokers and patients exposed to occupational air pollutants was high. Based on GOLD staging of severity of COPD, 14% were graded as mild, 63% were graded as moderate, 20% were graded as severe and 3% of patients had very severe form of COPD. Concomitant diseases like diabetes, hypertension and hyperthyroidism was found in 74.7% of the participants. Nearly 50% of the participants belong to very low socioeconomic status as per Modified Prasad Classification and medication cost was affordable only by 24.2%.  

Patient responses to COPD – Knowledge Questionnaire (COPD-Q) and its relation to medication adherence were summarized in Table 2.

Table 2. COPD Knowledge Questionnaire responses and its relation to medication adherence among study participants.

*p<0.05 - statistically significant.

There was no statistically significant association between individual knowledge questions and medication adherence except the question “COPD medicines prevent the disease from getting worse” (P=0.021). Average COPD-knowledge score was 6.23 ± 1.57.

Responses to medication adherence scale were summarized in Table 3.

Table 3. Responses to COPD medication adherence.

The adherent sum score ranged between 1-6, 43 (47%) participants who had a sum score of 6 were fully adherent to prescribed medications, 27 (30%) participants had a sum score of 5 and others had a sum score of 1-4 were partially adherent to prescribed medications. The overall medication adherence (range 1-6) among the participants was 81%.

Inhalational medications were used only by 43 (47.3%) patients. Responses to adherence to inhaled medications were summarized in Table 4.

Table 4. Responses to inhalational medication adherence.

MARS sum score was 23.55±3.95. Higher score indicates higher self-reported adherence. MARS sum score ranged between 5-25. Out of 43 patients, 39 (91%) had the sum score in the range of 21-25.

The common reasons for medication non-adherence were forgetfulness (82.5%), symptomatic relief of illness (12.5%), 10% responded that medicines got exhausted and 2.5% reported that it was socially inconvenient to take the medications.

CAT score of the patients and grading were summarized in Tables 5 and 6.

Table 5. COPD Assessment Test (CAT) – Individual item responses.

Table 6. Categorization of study participants based on CAT Score.

There was a statistically significant difference between adherent and partially adherent groups with respect to CAT score of the participants (Student’s t test; p value=0.020).

Highly adherent group was found to have high CAT score. (Table 7).

Table 7. Association between medication adherence score and CAT score.

Student’s t test; p value=0.020.

There was a statistically significant weak positive correlation (r=0.246) between medication adherence sum and CAT score.

Discussion

The patients in the present study had adherence to the medication at 47%. The percentage of adherence was less than the studies conducted in Hungary (58.2%) and Nepal (65%) (18,19). Although complete adherence was less than 50%, majority of the participants were partially adherent to the medications which was at 81% (Table-3). The most common cause for non-adherence was forgetfulness (82.5%). The percentage was very high when compared to other studies in which forgetfulness accounted for about 50% (15,19). 

There was a statistically significant association between medication adherence score and the CAT score similar to the study done by Kocakaya et.al. (20). The study had revealed better the adherence, better the quality of life. Though there is weak positive spearman’s correlation which was statistically significant, it may not be clinically significant. This can be overcome by increasing the sample size. Only 43 participants used inhalational medications and there was higher self-reported adherence to inhalational medications. That data is similar to a study done by Tommelein et al. (16).

In the tertiary care Institute where the study was conducted, patients with moderate and severe symptoms alone were advised to purchase inhaler and during inhaler introduction they were properly trained on how to use the inhaler. Further, compliance to the inhalational medications were checked during each follow-up. Since moderate to severe symptomatic patients were comfortable with inhalational medications, there was high degree of adherence to inhalational medications.

The patient’s COPD knowledge score was 6.23 ± 1.57. It was less when compared to the study done by Ray SM., et al. (7.6 ± 2.1) (14). Awareness of the patients on smoking and its association with COPD, reversal of COPD with quitting of smoking was only around 50% but comparable to prior studies (14). The percentage of COPD patients with smoking was only 22%. The results were similar to the study done by Mahmood T et.al., in which the percentage of nonsmokers with COPD was higher when compared to smokers with COPD (21). It was interesting to note that 100% of the participants were not aware about the importance of flu and pneumonia vaccination. It may be because of poor literacy rate and lack of awareness among the participants.

The results of our study are not surprising and consistent with prior studies. However, sociodemographic factors affect compliance. To our knowledge this is the first study to show the association between adherence and quality of life in COPD in a unique Indian population.

Conclusion

The study showed a statistically significant association between medication adherence and quality of life. Further studies evaluating the impact of education on medication adherence and quality of life are needed.  

References

1. Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary. Am J Respir Crit Care Med. 2017;195(5):557–82. [CrossRef] [PubMed]
2. Viegi G, Scognamiglio A, Baldacci S, Pistelli F, Carrozzi L. Epidemiology of chronic obstructive pulmonary disease (COPD). Respiration. 2001;68:4–19. [CrossRef] [PubMed]
3. World Health Organisation. Chronic obstructive pulmonary disease (COPD) [Internet]. WHO. [cited 2017 Dec 28]. Available from: http://www.who.int/respiratory/copd/en/ (accessed 6/18/19)
4. Toy EL, Beaulieu NU, McHale JM, et al. Treatment of COPD: Relationships between daily dosing frequency, adherence, resource use, and costs. Respir Med. 2011;105(3):435–41. [CrossRef] [PubMed]
5. Cazzola M, Dahl R. Inhaled Combination Therapy with Long-Acting β2-Agonists and Corticosteroids in Stable COPD. Chest. 2004;126(1):220–37. [CrossRef] [PubMed]
6. Rand CS, Nides M, Cowles MK, Wise RA, Connett J. Long-term metered-dose inhaler adherence in a clinical trial. The Lung Health Study Research Group. Am J Respir Crit Care Med. 1995;152:580–8. [CrossRef] [PubMed]
7. Kesten S, Flanders J, Serby CW, Witek TJ. Compliance with tiotropium, a once daily dry powder inhaled bronchodilator, in one-year COPD trials. Chest. 2000;118:191s– 192s.
8. Van Grunsven PM, Van Schayck CP, Van Deuveren M, Van Herwaarden CL, Akkermans RP, Van Weel C. Compliance during long-term treatment with fluticasone propionate in subjects with early signs of asthma or chronic obstructive pulmonary disease (COPD): results of the Detection, Intervention and Monitoring Program of COPD and Asthma (DIMCA) Study. J Asthma. 2000;37:225–34. [PubMed]
9. Krigsman K, Nilsson JL, Ring L. Refill adherence for patients with asthma and COPD: comparison of a pharmacy record database with manually collected repeat prescriptions. Pharmacoepidemiol Drug Saf. 2007;16:441–8. [CrossRef] [PubMed]
10. Bender BG, Pedan A, Varasteh LT. Adherence and persistence with fluticasone propionate/salmeterol combination therapy. J Allergy Clin Immunol. 2006;118:899-904. [CrossRef] [PubMed]
11. Breekveldt-Postma NS, Gerrits CMJM, Lammers JWJ, Raaijmakers J a. M, Herings RMC. Persistence with inhaled corticosteroid therapy in daily practice. Respir Med. 2004;98(8):752–9. [PubMed]
12. Montes de Oca M, Menezes A, Wehrmeister FC, et al. Adherence to inhaled therapies of COPD patients from seven Latin American countries: The LASSYC study. PLoS ONE. 2017;12(11):e0186777. [CrossRef] [PubMed]
13. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease: 2019 report. Available at: https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf (accessed 6/18/19).
14. Ray SM, Helmer RS, Stevens AB, Franks AS, Wallace LS. Clinical utility of the chronic obstructive pulmonary disease knowledge questionnaire. Fam Med. 2013;45(3):197–200. [PubMed]
15. Dolce JJ, Crisp C, Manzella B, Richards JM, Hardin JM, Bailey WC. Medication adherence patterns in chronic obstructive pulmonary disease. Chest. 1991;99(4):837–41. [PubMed]
16. Tommelein E, Mehuys E, Van Tongelen I, Brusselle G, Boussery K. Accuracy of the Medication Adherence Report Scale (MARS-5) as a quantitative measure of adherence to inhalation medication in patients with COPD. Ann Pharmacother. 2014;48(5):589–95. [CrossRef] [PubMed]
17. Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and first validation of the COPD Assessment Test. Eur Respir J. 2009;34:648-654. [CrossRef] [PubMed]
18. Agh T, Inotai A, Meszaros A. Factors Associated with Medication Adherence in Patients with Chronic Obstructive Pulmonary Disease. Respiration. 2011;82(4):328–34. [CrossRef] [PubMed]
19. Shrestha R, Pant A, Shakya Shrestha S, Shrestha B, Gurung RB, Karmacharya BM. A Cross-Sectional Study of Medication Adherence Pattern and Factors Affecting the Adherence in Chronic Obstructive Pulmonary Disease. Kathmandu Univ Med J. 2015;13(49):64–70. [PubMed]
20. Kocakaya D, Yıldızeli ŞO, Arıkan H, et al. The relationship between symptom scores and medication adherence in stable COPD patients. Eur Respir J. 2017;50(61):PA1062.
21. Mahmood T, Singh RK, Kant S, Shukla AD, Chandra A, Srivastava RK. Prevalence and etiological profile of chronic obstructive pulmonary disease in nonsmokers. Lung India. 2017;34(2):122–6. [CrossRef] [PubMed]

Cite as: kumar S KS, Maharni B, Babu RV, Prakash M. Adherence to prescribed medication and its association with quality of life among COPD patients treated at a tertiary care hospital in Puducherry – a cross sectional study. Southwest J Pulm Crit Care. 2019;18(6):157-66. doi: https://doi.org/10.13175/swjpcc021-19 PDF 

June 2019 Pulmonary Case of the Month: Try, Try Again

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 53-year-old woman from presented with a 3-year history of shortness of breath. She was diagnosed with pneumonia in 2016, but even after treatment with antibiotics, continued to require supplemental oxygen. A CT-guided biopsy of a lung nodule was performed but there were no diagnostic findings. A surgical lung biopsy at another hospital was done but the report is unavailable. She had been diagnosed with possible scleroderma and treated with mycophenolate for 3 months and then azathioprine. 

Past Medical History, Social History and Family History

Aside from her history as in the HPI she has a remarkably negative past medical history. She does not smoke. Family history is noncontributory.

Physical Examination

• HEENT:  negative
• Chest:  Fine crackles at both lung bases
• Cardiovascular: regular rhythm, no murmur
• Skin:  skin thickening on fingers and distal forearms, but not elsewhere.  No pitting, ulcerations or calcinosis

Radiology

A chest x-ray was performed (Figure 1).

Figure 1. PA chest radiography done on presentation.

Which of the following should be done? (Click on the correct answer to be directed to the second of six pages)

1. Obtain previous radiography and biopsy reports
2. Pulmonary function testing
3. Thoracic CT scan
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. June 2019 pulmonary case of the month: Try, try again. Southwest J Pulm Crit Care. 2019;18(6):144-51. doi: https://doi.org/10.13175/swjpcc026-19 PDF

Update and Arizona Thoracic Society Position Statement on Stem Cell Therapy for Lung Disease

Summary

Infusions of stem cells are increasingly being offered for a variety of diseases, including chronic lung diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and cystic fibrosis. However, the potential for harm, the lack of any proven benefit, and the high fees that many of these programs charge make recommending stem cell therapy untenable. At the time of this writing (April 2019) it appears that stem cell therapy can be safely performed, although the long-term side effects remain unknown. However, the little data available show no benefit in meaningful outcomes, such as mortality, morbidity or patient well-being, for stem cell treatment of chronic lung disorders. Patients with severe, incurable diseases may be motivated to seek innovative therapies. We encourage such patients to contact their primary care physician or pulmonologist. Clinical trials in the United States and Canada investigating stem cell therapy for lung diseases can be found on the website of the National Institutes of Health at Clinicaltrials.gov. The Arizona Thoracic Society encourages regulatory agencies to protect the public health and take appropriate action against non-investigational, for-profit stem cell clinics when appropriate.

Introduction

A central component of the mission of medical societies is to translate new scientific information into patient education. There appears to be increasing direct-to-consumer advertising of untested, unapproved, and potentially ineffective “stem-cell” treatments for a variety of diseases, including lung disorders (1). One may come across information regarding stem cell therapy for chronic obstructive pulmonary disorders and fibrotic lung disease, in the United States and worldwide, on the internet, patient support groups, or other sources. Recently, a direct mailing to the home of one of the members of the Arizona Thoracic Society was received (Figure 1).

Figure 1. Direct mailing for stem cell therapy for several diseases including COPD received by one of the members of the Arizona Thoracic Society.

These programs are often characterized by:

• Exorbitant fees
• Misrepresentation of risks and benefits
• Overreliance on, and advertisement of, patient testimony
• Poor patient follow-up
• Absence of regulatory oversight and objective clinical evidence for claimed benefits

Therefore, they differ substantially from therapies approved by legitimate regulatory agencies, from well-designed, controlled, and appropriately regulated clinical trials, and from regulated compassionate use of innovative cell therapies.

Chronic Obstructive Pulmonary Disease (COPD)

Stem cells can differentiate into several different lung cell types, including the alveolar epithelial cells. Since COPD is a disease associated with destruction of alveoli induced by cigarette smoke, the concept of rebuilding the alveoli through stem cell therapy is attractive. Pre-clinical trials in animal models have suggested regeneration of alveolar-like structures, repair of emphysematous lungs, and reduction of inflammatory responses, with the greatest success being in acute lung injury models.

Currently, regenerative therapies are divided into extrinsic therapeutic strategies and intrinsic cell therapy methods. Extrinsic cell therapy refers to the vascular infusion of (or endotracheal installation) of stem cells, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSs), mesenchymal stem cells (MSCs), and human lung stem cells (hLSCs). Intrinsic therapy refers to the delivery of small molecules (retinoid compounds have been the most studied) that can stimulate the endogenous lung stem/progenitor cells to regenerate and replace damaged structures.

A number of recent review articles have summarized the current state of research in the use of stem cells in COPD (2-4). These review articles all contain summaries of trials conducted to date using both extrinsic and intrinsic therapies. There have been several phase I clinical trials, primarily assessing safety, and a handful of small phase II clinical trials that have been negative for meaningful clinical outcomes. Sun et al. (3) point out that the available trials have all been conducted on patients with advanced COPD. The authors suggest that further research is required on how to enhance the engraftment of exogenous mesenchymal stem cells in damaged lungs. Further, considering the anti-inflammatory and immunomodulatory effects of exogenous mesenchymal stem cells, they may be most effective potentially in treating acute lung disease, as opposed to chronic progressive disease with severe structural damage.

Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive debilitating lung disease of unknown etiology characterized by a combination of histological changes, including extracellular matrix (ECM) deposition, phenotypic changes of fibroblasts, and alveolar epithelial cells, the formation of fibroblastic foci, and scattered areas of aberrant wound healing interspersed with normal lung parenchyma (5).

There are two approved compounds for the treatment of IPF: pirfenidone and nintedanib. Pirfenidone is an antifibrotic compound with an unclear mechanism of action, targeting several molecules, including transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and interleukin 6 (6). Nintedanib is a tyrosine-kinase inhibitor, targeting vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet derived growth factor receptor (PDGFR) (7). While the use of pirfenidone and nintedanib has been shown to slow the progression of IPF, neither is curative and morbidity and mortality from IPF remains high (8,9).

Because of the inadequacy of therapy in IPF, the use of mesenchymal stem cells (MSCs) has attracted interest as a potential option. Early clinical studies have shown that the MSCs can be safely administered (5,10-12). A phase Ib study of endobronchially administered autologous adipose-derived MSCs showed not only acceptable safety outcomes, but also improvements in quality of life parameters (12). However, there were no significant differences in any of the studied functional parameters (FVC, FVC%pred. and DLCO% pred.) at baseline and 6 and 12 months following 3 endobronchial infusions of MSCs.

Cystic Fibrosis

Cystic fibrosis (CF) is a genetic syndrome usually resulting in a high mortality rate due to progressive lung disease. Several drugs targeting specific mutated cystic fibrosis transmembrane regulator (CFTR) proteins are already in clinical trials. However, new therapies, based on stem cells, are also emerging. Interest has focused on induced pluripotent stem (iPS) cells. It is possible to make iPS cells using cells from people with CF, and then use gene editing to correct CFTR mutations in those cells (13). This suggests the possibility of re-implanting the corrected iPS cells into the lungs of people with CF to generate healthy lung cells. Currently, three trials examining the safety of stem cells in cystic fibrosis are ongoing according to Clinicaltrials.gov. 

Adult Respiratory Distress Syndrome (ARDS)

Four clinical trials are listed on Clinicaltrials.gov for ARDS and stem cells; one, which involved 3 patients, has been completed (14). No outcome information is available.

Other Lung Diseases

We are unaware of any human trials at this time with outcomes in other lung diseases.

Regulatory and Legal Actions

The Food and Drug Administration (FDA) and the Attorney General of New York have both expressed concern over stem cell therapy. The concerns follow reports of three patients becoming blind after receiving injections of stem cells into the eye and twelve patients who became seriously ill after receiving injections that purportedly contained stem cells from umbilical cord blood (15,16). The FDA has issued warning letters to stem cell clinics, including one letter claiming violation of Federal law, and another 20 warnings to clinics of that their claims and actions were subject to FDA approval. The NY Attorney has filed a lawsuit against a for-profit stem cell clinic, Park Avenue Stem Cell, claiming it performed unproven procedures on patients with a wide range of medical conditions, from erectile dysfunction to heart disease (17).

The Arizona Thoracic Society encourages further investigation into stem cell transplantation in lung disease. However, we do not at this time encourage non-investigational use of stem cells since the therapy has not been shown to have meaningful patient benefits. We also encourage state and local regulatory agencies in the Southwest to protect the public health and take appropriate action against non-investigational, for-profit stem cell clinics when appropriate.

References

1. American Lung Association. Statement on Unproven Stem Cell Interventions for Lung Diseases (July 2016). Available at: https://www.thoracic.org/members/assemblies/assemblies/rcmb/working-groups/stem-cell/resources/statement-on-unproven-stem-cell-interventions-for-lung-diseases.pdf (accessed 4/5/19).
2. Balkissoon R. Stem Cell Therapy for COPD: Where are we? Chronic Obstr Pulm Dis. 2018;5(2):148-53. [CrossRef] [PubMed]
3. Sun Z, Li F, Zhou X, Chung KF, Wang W, Wang J. Stem cell therapies for chronic obstructive pulmonary disease: current status of pre-clinical studies and clinical trials. J Thorac Dis. 2018 Feb;10(2):1084-98. [CrossRef] [PubMed]
4. Cheng SL, Lin CH, Yao CL. Mesenchymal Stem Cell Administration in Patients with Chronic Obstructive Pulmonary Disease: State of the Science. Stem Cells Int. 2017;2017:8916570. [CrossRef] [PubMed]
5. Tzouvelekis A, Toonkel R, Karampitsakos T, Medapalli K, Ninou I, Aidinis V, Bouros D, Glassberg MK. Mesenchymal stem cells for the treatment of idiopathic pulmonary fibrosis. Front Med (Lausanne). 2018 May 15;5:142. [CrossRef] [PubMed]
6. Kolb M, Bonella F, Wollin L. Therapeutic targets in idiopathic pulmonary fibrosis. Respir Med. 2017;131:49–57. [CrossRef] [PubMed]
7. Fletcher S, Jones MG, Spinks K, et al. The safety of new drug treatments for idiopathic pulmonary fibrosis. Expert Opin Drug Saf. 2016;15:1483–9. [CrossRef] [PubMed]
8. King TE, Bradford WZ, Castro-Bernardini S, et al. Phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083–92. [CrossRef] [PubMed]
9. Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071–82. [CrossRef] [PubMed]
10. Tzouvelekis A, Ntolios P, Karampitsakos T, et al. Safety and efficacy of pirfenidone in severe idiopathic pulmonary fibrosis: a real-world observational study. Pulm Pharmacol Ther. 2017;46:48-53. [CrossRef] [PubMed]
11. Tzouvelekis A, Koliakos G, Ntolios P, et al. Stem cell therapy for idiopathic pulmonary fibrosis: a protocol proposal. J Transl Med. 2011;9:182. [CrossRef] [PubMed]
12. Tzouvelekis A, Paspaliaris V, Koliakos G, et al. A prospective, non-randomized, no placebo-controlled, phase Ib clinical trial to study the safety of the adipose derived stromal cells-stromal vascular fraction in idiopathic pulmonary fibrosis. J Transl Med. 2013;11:171. [CrossRef] [PubMed]
13. The Cystic Fibrosis Foundation. Stem cells for cystic fibrosis therapy. Available at: https://www.cff.org/Research/Research-Into-the-Disease/Restore-CFTR-Function/Stem-Cells-for-Cystic-Fibrosis-Therapy/ (accessed 4/5/19).
14. Clinicaltrials.gov. Human Mesenchymal Stem Cells For Acute Respiratory Distress Syndrome (START). Available at: https://www.clinicaltrials.gov/ct2/show/results/NCT01775774?term=Stem+cells&cond=ARDS&rank=4 (accessed 4/5/19).
15. Kuriyan AE, Albini TA, Townsend JH, et al. Vision loss after intravitreal injection of autologous "stem cells" for AMD. N Engl J Med. 2017 Mar 16;376(11):1047-53. [CrossRef] [PubMed]
16. Grady D. 12 People hospitalized with infections from stem cell shots. NY Times. Dec. 20, 2018. Available at: https://www.nytimes.com/2018/12/20/health/stem-cell-shots-bacteria-fda.html?action=click&module=RelatedCoverage&pgtype=Article&region=Footer (accessed 4/9/19).
17. Abelson R. N.Y. attorney general sues Manhattan stem cell clinic, citing rogue therapies. NY Times. April 4, 2019. Available at: https://www.nytimes.com/2019/04/04/health/stem-cells-lawsuit-new-york.html (accessed 4/9/19).

Cite as: Arizona Thoracic Society*. Update and Arizona Thoracic Society position statement on stem cell therapy for lung disease. Southwest J Pulm Crit Care. 2019;18(4):82-6. doi: https://doi.org/10.13175/swjpcc020-19 PDF

*The below contributed to the update and position statement on stem cell therapy

• Bhargavi Gali, MD
• Michael B. Gotway, MD
• Kenneth S. Knox, MD
• Timothy T. Kuberski, MD
• Stuart F. Quan, MD
• George Parides, DO
• Richard A. Robbins, MD
• Gerald F. Schwartzberg, MD
• Allen R. Thomas, MD
• Lewis J. Wesselius, MD

March 2019 Pulmonary Case of the Month: A 59-Year-Old Woman with Fatigue

Lewis J. Wesselius, MD¹

Michael B. Gotway, MD²

¹Department of Pulmonary Medicine and ²Department of Radiology

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 59-year-old woman from Kingman, Arizona had a one-year history of fatigue with some shortness of breath. For this reason, she saw her primary care physician.

Past Medical History, Social History and Family History

She has no significant past medical history. She does not smoke. Family history is noncontributory.

Physical Examination

Physical examination was unremarkable.

Which of the following should be done? (Click on the correct answer to be directed to the second of seven pages)

1. Chest x-ray
2. Complete blood count
3. Electrolytes, blood urea nitrogen and creatinine
4. Liver panel
5. All of the above

Cite as: Wesselius LJ, Gotway MB. March 2019 pulmonary case of the month: A 59-year-old woman with fatigue. Southwest J Pulm Crit Care. 2019;18(3):52-7. doi: https://doi.org/10.13175/swjpcc008-19 PDF 

Co-Infection with Nocardia and Mycobacterium Avium Complex (MAC) in a Patient with Acquired Immunodeficiency Syndrome

Zahira Babwani DO

Kenneth Wojnowski Jr DO

Sunil Kumar MD

Broward Health Medical Center

Fort Lauderdale, FL USA

Abstract

We present a case in which a patient with acquired immunodeficiency syndrome (AIDS) and nocardiosis was found to have co-infection with Mycobacterium avium complex (MAC). Despite the fact that MAC is a known colonizer of the pulmonary system, ​ it is possible to have co-infection and a high degree of suspicion is necessary to ensure prompt treatment of both organisms. We wish to describe how radiologic findings were instrumental in guiding our differential diagnosis.

Case Report

History of Present Illness​: A 64-year-old man with history of alcohol and tobacco abuse presented with a chronic, productive cough for 5-6 months. Associated symptoms included shortness of breath and 30-pound weight loss. He denied all other symptoms.

Physical Exam​: Pertinent positives revealed temporal wasting, poor dental hygiene, oral thrush and diffuse rhonchi bilaterally. Initial vital signs were within normal limits.

Laboratory and Radiology​: Pertinent laboratory findings revealed leukocytosis with a left shift. Viral respiratory polymerase chain reaction (PCR) testing was negative. Human immunodeficiency virus (HIV) testing was positive with a CD4 count of 46 cells/mm³. QuantiFERON gold testing was negative. Sputum cultures, acid-fast bacilli (AFB) and blood cultures were obtained. Bronchoalveolar lavage (BAL) was performed with no evidence of Pneumocystis jirovecii (PJP). Chest X-ray (CXR) and computed tomography (CT) of the chest (Figure 1) revealed a multifocal right lung abscess with complex pleural fluid, empyema, nodular cavitary lesion in the left lower lobe and hilar lymphadenopathy.

Figure 1. Panel A: initial chest X-ray shows a complex infiltrate and effusion in the right lung. There is a cavitary lesion with air-fluid level vs lung abscess on the right. A nodule or consolidation is present in the left lung base. Panel B: A representative image from the initial CT of the chest showing a multifocal right lung abscess and complex pleural fluid.

Hospital Course: ​After admission, the patient was started on broad spectrum antimicrobials with vancomycin and piperacillin-tazobactam. A thoracentesis was performed due to right sided pleural effusion which yielded 65 cc of thick, purulent, green fluid. Thoracotomy with complete decortication of the right lung was performed with biopsies of the abscesses. Two 32-French chest tubes were placed due to the presence of multiple intraparenchymal lung abscesses, loculations, and empyema. Biopsy and pleural fluid cultures grew gram positive, beaded organisms which were later identified as nocardia, with no evidence of MAC or Mycobacterium tuberculosis (MTB). The patient was started on amikacin, meropenem and trimethoprim-sulfamethoxazole for newly diagnosed pulmonary nocardiosis. MAC prophylaxis was initiated due to his low CD4 count. After initiation of therapy for nocardiosis, three sputum AFB cultures began to stain positive. Since nocardiosis stains weakly positive for AFB, we initially did not suspect non-tuberculous Mycobacteria (NTM). Repeat CT scan of the chest (Figure 2) revealed ground glass opacities, nodular densities and both mediastinal and hilar lymphadenopathy.

Figure 2. Panel A: after initiation of treatment for nocardiosis, improvement of right empyema and cavitary lesion with bilateral patchy airspace disease right greater than left. Panel B: CT of the chest after initiation of treatment for nocardiosis, prominent lymph nodes in the hilar regions and mediastinum. less cavitation than the previous study. There are innumerable ground glass and nodular densities throughout both lungs, right greater than left.

Suspicion for active MAC co-infection was raised, the prophylactic dose of azithromycin was increased to the treatment dose, and ethambutol was initiated. After three weeks of intravenous amikacin, meropenem and trimethoprim-sulfamethoxazole the patient showed considerable improvement in his respiratory symptoms and was transitioned to oral trimethoprim-sulfamethoxazole for outpatient treatment of nocardiosis with continuation of ethambutol and clarithromycin for MAC.

Discussion

The Mycobacterium Avium Complex ​(MAC) is a Non-tuberculous mycobacterium (NTM) that is commonly found in patients with HIV and a CD4 count of less than 50. The diagnosis of NTM is challenging due to the fact that the organism is a known colonizer of the pulmonary system (1) ​. Supportive radiologic evidence is needed to distinguish colonization from active infection (2).

Common CT findings of nocardiosis include ground glass opacities, lung nodules, cavitation, pleural effusion and masses (3)​. The presence of mediastinal and hilar lymphadenopathy is the most common finding in immunosuppressed patients with MAC infection but is not​ a usual feature of pulmonary nocardiosis (3,4) ​. Our​ patient’s repeat CT scan showed mediastinal and hilar lymphadenopathy with improvement of cavitary lesions which suggests improvement of CT findings related to nocardiosis, but persistent findings related to NTM (5). This led us to believe that the patient was appropriately treated for nocardiosis, but with an underlying presence of active MAC infection that presented with atypical radiographic findings. As per the American Thoracic Society (ATS) guidelines for NTM pulmonary infection (6)​ ​, this patient’s pulmonary symptoms, radiological evidence on the chest CT, and positive AFB cultures from at least two separate expectorated sputum samples lends credibility to MAC as a true active infection in the setting of nocardiosis and AIDS. The patient was appropriately placed on clarithromycin and ethambutol as an outpatient, and our suspicions were confirmed for MAC with no evidence of MTB by PCR testing 5 weeks after initial AFB smears were collected.

Co-infection with Nocardiosis and MAC may be underestimated since they both often develop in immunocompromised hosts. MAC, along with other NTM species account for 20% of mycobacterium pulmonary infections in HIV infected patients (5)​. Nocardia accounts for less than 3% of pulmonary infections in HIV infected patients (5)​. A high degree of clinical suspicion is imperative to promptly treat infection with both organisms.

References

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Cite as: Babwani Z, Wojnowski K Jr, Kumar S. Co-Infection with Nocardia and Mycobacterium avium complex (MAC) in a patient with acquired immunodeficiency syndrome. Southwest J Pulm Crit Care. 2019;18(1):22-5. doi: https://doi.org/10.13175/swjpcc123-18 PDF