Association between Absolute Eosinophils Counts & Acute Exacerbation of COPD.

Association between Absolute Eosinophils Counts & Acute Exacerbation of COPD.

Dr.Krupa Rajeshkumar Shah 1*, Dr.Sanjay Tripathi 2 Dr.Vishakha Kapadia 3, Dr.Rajdeep Dhandhukiya 4 ,   Dr Sahil Nayee 5

1. Dr.Krupa Rajeshkumar Shah (3rd Year Resident Pulmonary Medicine) NHLMMC Ahmedabad.

2. Dr.Sanjay Tripathi (PG Teacher &HOD)

3. Dr.Vishakha Kapadia (Associate Professor)

4. Dr.Rajdeep Dhandhukiya(Assistant Professor)

5. Dr Sahil Nayee (2nd Year Resident Pulmonary Medicine)

Correspondence to: Dr.Krupa Rajeshkumar Shah, B/G 1 Ramtirth flat Naroda Dhegan Road, Ahmedabad 382330, Gujarat.

Copyright

© 2024 Dr.Krupa Rajeshkumar Shah. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 05 April 2024

Published: 01 May 2024


Association between Absolute Eosinophils Counts & Acute Exacerbation of COPD.

INTRODUCTION

• Chronic Obstructive Pulmonary Disease (COPD) Is a Common Disease That Is Characterized By Persistent Respiratory Symptoms And Airflow Limitation. Due To Abnormalities Of The Airway Or Alveoli Or Both Caused By Exposure To Noxious Particles And Gases[1].COPD is a leading cause of morbidity and mortality world wide (3 most common causes of death world wide and 90% of death occurs in low -middle income countries).[2]

• Acute exacerbation COPD can occur due to multiple causes including infectious causes (viral and bacterial respiratory tract infection) and non infectious causes air pollution , biomass exposure , drug default. Around 10- 40% of COPD exacerbation are due to TH2 mediated- Eosinophilic airway inflammation[3]. The mechanism by which eosinophilic inflammation may contribute to exacerbations is unclear, but it may be a combination of oedema, airway remodelling, mucus production and changes in airway geometry.[4]

• AEC (Absolute eosinophils count) it represents the actual number of eosinophils per microliter of blood . the absolute count is the percentage of Eosinophils multiplied by white blood count(WBCs) . Normal rages is between 30-350 cells/microliter of blood.

 • Currently, the best predictor of COPD exacerbation is a previous history of exacerbation[5]. It is clear that a subset of COPD patients has raised eosinophil levels [6], and that having higher eosinophil levels may be associated with an increased risk of exacerbations [7].

 

AIMS AND OBJECTIVES

• To assess the relationship between blood eosinophils level and COPD exacerbations.

• The comparison of clinical outcome between normal AEC ranges group and elevated AEC groups


ELIGIBILITY

INCUSION CRITERIA-

• Male or female above 40 years of age.

• A patient diagnosed with Chronic Obstructive Lung Disease according to GOLD guideline (Post bronchodilator- FEV1/FVC <70%)

• Patient who has severe exacerbation of COPD according to GOLD 24 who needed hospitalization.

 

EXCLUSION CRITERIA-

•           Bronchial asthma or ABPA patients

•           Asthma COPD overlap syndrome

•           H/O allergy or hypersensitivity

•           H/O parasitic infections

•           Hyper eosinophilic syndrome

 

METHODOLOGY

• Retrospective Observation study In Department Of Respiratory medicine In SVP Hospital Ahmedabad in duration of 1 year( From December 2022 To NOVEMBER 2023)in patient who was admitted with exacerbation of COPD whose baseline stable state Absolute eosinophil count values were available.

• Patients who were diagnosed case of COPD by clinical history, exposure and occupation history and whose PFT post bronchodilator FEV1/FVC <70% according to Global Initiative For Chronic Obstructive Lung Disease (GOLD) Guideline 2023 were taken for the study. Exacerbation of COPD as defined by GOLD 2023 – patients with dyspnoea and/or cough and sputum production that worsen over <14 days with tachycardia and /or tachypnoea with signs of local and systemic inflammation were considered.

 

According to this patient who was needed hospital admissions were admitted.

• We extracted the following data from the medical records: patients’ demographics, the history of hospital admissions in the previous year, laboratory data (eosinophil counts during stable COPD and AECOPD at the time of hospital admission),duration of hospital stay, admission to the intensive care unit (ICU), length of ICU stay, any need for Non invasive ventilation &The duration of for Non invasive ventilation mechanical ventilation & the duration of mechanical ventilation and treatment outcomes(discharge and death).

• The cut of value for AEC ≤ 300 CU/MM were considered normal.

• Values were compared of Eosinophilic (>300 cu/mm)and Non-eosinophilic (<300 cu/mm)groups.

 

OBSERVATION & RESULTS-

• Baseline demographics and clinical outcomes were compared between patients with normal AEC and raised AEC during the exacerbations.

• From total 1 year of duration 86 patient had exacerbation of COPD , 56 patient’s baseline absolute eosinophils count in stable stat were available, these patients were included for the study.

• From total 56 patients- 51(91%) patients were male and 5 (9%)were

female. Median age group in eosinophilic and non eosinophilic group was respectively was 65.87 and 64.71 years.

 • From 56 Patients 54(96%) patients had AEC Within Normal Range And 2(4%) Patients Had Elevated AEC in stable state .From 56 patient only 7 (12.5%) patients had elevated AEC and 49(87.5%)patients still had within limit values AEC during exacerbations.

• In comparison with stable state , during exacerbation AEC was increased only in 7 (12.5%) patients from total 56 patients , with 2(4%) patient having baseline elevation during the stable state.

• From this 56 patients 10 (17.85%) patient had previous h/o exacerbation from     7 from the AEC group <300(14.28%) and 3(42.85%) from the >300 group.

• Average hospital stay during exacerbation in normal and raised AEC group was almost equal respectively 7 and 6 days. From normal AEC group 10 (17.85%) patient required ICU admission , from this 5 required non invasive ventilation(NIV) and 5 required Mechanical ventilation. From raised AEC group 1 patient required ICU admission and was kept on non invasive ventilation(NIV ).Total 2 patient died that belonged to normal AEC Group, no mortality noted in AEC > 300 group. with 47(83.92%) getting discharged in AEC<300 and 7(12.5%)in AEC >300.

 

Baseline characteristic and clinical outcome during exacerbation of COPD.

 

AEC <300

AEC>300

p value

SEX(n total -56)

 

 

 

 

MALE (n -51)

45(80.35%)

6(10.71%)

 

 

FEMALE(n-5)

4(7.14%)

1(1.78%)

 

 

Average age (in years)

65.87

64.71

 

 

Previous h/o of exacerbation

7(14.28%)

3(42.85%)

0.064

 

CLINICAL OUTCOME

n-49

n-7

0.047

 

Average days of

hospitalization(in days)

7(5-9 )

6(5-8)

 

 

ICU admission

10(10.26%)

1(14.28%)

0.70

 

Non invasive ventilation

5(50 %)

1(14.28%)

0.129

 

Mechanical ventilation

5(50%)

0

0.044

 

 

TREATMENT OUTCOME

 

1

DISCHARGE

47(95.91%)

7(100%)

 

DEATH

2(4.08%)

0

 

 

AEC( in cu/mm)

STABLE

EXACERBATION

P VALUE-0.1617

≤300

54 (96%)

49(87.5%)

 

>300

2 (4%)

7(12.5%)

 

 

• In our study We applied chi square test in the comparison of previous history of exacerbation we got p value of 0.064(>0.05)which is non- significant -no increased risk of exacerbations with AEC values.

• In clinical outcome(days of hospitalization and need of ICU admission) we got p value of 0.047 which is significant suggestive of increased risk of admission and hospital stay in AEC <300 group.

• There is no increased risk of requirement of icu admission (p value 0.68- non significant) but requirement of mechanical ventilation is significant with p vale of 0.044.

• In treatment outcome(discharge and death) p value is 1 which non- significant suggestive of no increased risk of death in aec group<300.

• Also there is no significant relation ship between the AEC value in stable state and during the exacerbation.


DISCUSSION-

• The association between eosinophilic inflammation of COPD, its dynamics and exacerbation risk are controversial. Schumann et al. suggested that blood eosinophil levels are variable throughout the course of COPD and phenotyping are difficult based on a single measurements [11]. In the ECLIPSE study, half of the patients were an intermittent group with variable eosinophil counts that oscillated above and below 2%, the results of the ECLIPSE study, in which only 13.6% of subjects had persistently low blood

eosinophils, and 49% and 37.4% had variable and persistently high blood eosinophils, respectively [12]. However, Kim et al. reported that blood eosinophils at a time-point were a useful predictor of being in the persistent eosinophilia group over the next 12 months demonstrating longitudinal stability of blood eosinophilic infammation within individuals [13].

• The reference was taken from the paper published Marc Miravitlles et al

[8] and The article published Dave Singh et at[9]in both the studies they did not find a clinically important relationship between baseline blood eosinophils count and exacerbation rate.

• Another reference study was taken from the paper published Hye seon kang et al[10]they found positive corelation between eosinophil count and exacerbation COPD.

• Comparing our study with et at[9] & et al [10]

 

DEMOGRAPHY

 

Our study

 

 

et al [9]

 

Hye seon

Et al 10

 

 

 

Dave

 

AEC

<300

>300

 

<300

>300

 

<300

>300

 

 

n-49

n-7

 

n-

17,677

n-

4448

 

n-299

n-48

 

MALE

45

6

 

12904

3584

 

217

37

 

Mean age

65.87

64.71

 

65.15

64.6

 

73.36

68.79

 

Previous history of

exacerbation

6

4

0.037

3050

766

 

95

11

0.216

 

CLINICAL OUTCOME

 

Average days of

admission(in days)

7(5-9 )

6(5-8)

 

-

-

 

8(6-12)

5.5(3.25-

9.5)

 

ICU

10

1

0.70

-

-

 

28

2

0.234

NIV

5

1

0.129

-

-

 

5

0

0.367

Mechanical

ventilation

5

-

0.044

-

-

 

22

2

0.419

Resolve

47

7

1

-

-

 

286

47

0.459

Death

2

-

 

-

-

 

13

1

0.459

 

• Some comparison between our study with study Dave Singh et al[ 9] and Hye seon kang et al [10], in all this studies previous history of exacerbation were noted more in AEC<300 group, so currently previous history of exacerbation tends to more potent indicator . In a recent study analysing data from the ECLIPSE and the COPDGene cohorts, a blood eosinophil concentration > 300 cells/l was a good predictor of future risk of exacerbations only in patients with frequent exacerbations, but not in patients with 0 or 1 exacerbation in the previous year

• Also the need of ICU admission as well need of mechanical and non

invasive ventilation found to be more required in group of AEC <300 In our study and study Hye seon kang at al [10]

• In comparison with the above study exacerbation was found more in normal eosinophilic population , days of hospitalization is almost equal in both group, need of ICU admission and mechanical ventilation requirement was more observed in normal AEC group.

 

CONCLUSION-

• We Found No Clinically Important Relationship Between Baseline Blood Eosinophil Count And Exacerbation Rate. Hence, The Current Analysis Does Not Support The Use Of Blood Eosinophils To Predict Exacerbation Risk and as well as to be used as biomarker.

 

Pitfalls-

• Large study population would provide better outcome.

• Further studies are necessary to determine whether those with persistently high eosinophils during short-term follow-up (i.e., 6 months) have

consistent results.

 

Abbreviations-

AEC- absolute eosinophil count

COPD -chronic obstructive pulmonary disease AECOPD- acute exacerbation of COPD

ICU-intensive care unit

NIV non invasive ventilation

 

REFERENSES

[1,2]GOLD 2023-

FISHMAN TEXTBOOK OF PULMPONARY MEDICINE CHAPTER 37 & 38.

 [3] 1. Saha S, Brighting CE. Eosinophilic airway inflammation in COPD Int J Chron Obstruct Pulmon Dis. 2006;1(1):39-47. doi:10.2147/ copd.2006.1.1.39

 [4]O. Eltboli, C.E. Brightling, Eosinophils as diagnostic tools in chronic lung disease, Expert Rev. Respir. Med. 7 (1) (2013) 33-42.

[5]- J.R. Hurst, J. Vestbo, A. Anzueto, N. Locantore, H. Mullerova, R. Tal-Singer, et al., Susceptibility to exacerbation in chronic obstructive pulmonary disease, N. Engl. J.Med. 363 (12) (2010) 1128-1138.

[6]- M. Bafadhel, S. McKenna, S. Terry, V. Mistry, C. Reid, P. Haldar, et al., Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers, Am. J. Respir. Crit. Care Med. 184 (6) (2011) 662-671

[7]- S. Vedel,krogh s.f Nielsen . P lange , J vestbo , B.G. Nordestgard, Blood eosinophils and exacerbation in COPD the coperhegan general population study Am. J. Respair .Crit. Care Med. 193 (9) (2016) 965-974.

[8]Blood Eosinophil Counts and Their Variability and Risk of Exacerbations in COPD: A Population-Based Study-

[9]Blood eosinophils as a biomarker of future COPD exacerbation risk: pooled data from 11 clinical trials- https://respiratory-research.biomedcentral.com/counter/pdf/10.1186/s12931-020-01482-1.pdf

[10]The association between eosinophilic exacerbation and eosinophilic levels in stable COPD- https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-021-01443-4

[11] Schumann DM, Tamm M, Kostikas K, Stolz D: Stability of the blood eosinophilic phenotype in stable and exacerbated COPD. Chest 2019

[12] Singh D, Kolsum U, Brightling CE, Locantore N, Agusti A, Tal-Singer R. Investigators E: Eosinophilic infammation in COPD: prevalence and clinical characteristics. Eur Respir J. 2014;44(6):1697–700

 [13] Kim VL, Coombs NA, Staples KJ, Ostridge KK, Williams NP, Wootton SA, Devaster JM, Aris E, Clarke SC, Tuck AC, et al. Impact and associations of eosinophilic infammation in COPD: analysis of the AERIS cohort. Eur Respir J. 2017;50(4):1700853.

[14]Blood eosinophil levels as a biomarker in COPD- Respiratory Medicine 138 (2018) 21–31- https://www.resmedjournal.com/article/S0954-6111(18)30080-5/fulltext

[15]https://www.thelancet.com/journals/lanres/subscribe?backUri=%2Fjournals%2Flanres%2Farticle%2FPIIS221 3- 2600%2817%2930217-5%2Ffulltext&offerId=302562%2C10.1016%2FS2213 2600%2817%2930217- 5&addToCart=true

[16]Blood Eosinophils and Chronic Obstructive Pulmonary Disease: A Global Initiative for Chronic Obstructive Lung Disease Science Committee 2022 Review | American Journal of Respiratory and Critical Care Medicine (atsjournals.org)

[17]Siva R, Green RH, Brightling CE, et al. Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial. Eur Respir J 2007;29:906-13. [Crossref] [PubMed]

[18]Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease -PMC (nih.gov) 

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