Are higher levels of lipid profile parameters associated with increased chances of uncontrolled asthma among adults?

ABSTRACT

Background:

Studies on the relationship between asthma and various parameters of fasting lipid profile have reported conflicting results. In this study, we intend to explore this association between asthma and its level of control with fasting serum lipid profile further.

Methods:

In our observational prospective cohort study, we studied 107 known asthmatic patients presenting in large tertiary care centre of North India. Fasting serum samples for lipid profile reports of all patients were collected. Patients were divided into controlled and uncontrolled asthma groups on the basis of clinical symptoms and spirometric findings. We evaluated the statistical difference and significance for various lipid profile parameters in between two groups using an independent t-test.

Results:

On comparing the fasting lipid profile of 38 patients with uncontrolled asthma and 69 patients with controlled asthma, we found that serum levels of low-density lipoprotein (LDL) and ratio of total cholesterol to high-density lipoprotein (TC: HDL) were significantly higher among patients with uncontrolled asthma. On statistical analysis, their P values were 0.03 and 0.047, respectively.

Conclusion:

Serum levels of LDL and ratio of TC: HDL were higher in patients with uncontrolled asthma.

INTRODUCTION

Asthma is a heterogenous disease, usually characterized by chronic airway inflammation. There are different types of asthma phenotypes, with different underlying pathogenic processes.[1] Chronic airway inflammation that is characteristic of asthma can be caused by various allergens and obesity.[2] Asthma exhibits two different disease entities: environmental allergen-related atopic asthma and allergen not-related non-atopic asthma.[3] In contrast to atopic asthma, non-atopic asthma often responds poorly to inhaled or oral corticosteroids and tends to be related to more severe disease.[4] Metabolic syndrome and dyslipidemia, which are known to contribute to a pro-inflammatory state, have attracted interest as a potential cause of non-atopic asthma in recent years.[2,5] Several studies investigating the relationship between lipid profiles and asthma still have reported different results. Among school children in Taiwan, asthma was found to be associated with higher low-density lipoprotein cholesterol (LDL-C) levels.[6] However, a large study of the US population demonstrated through a nationally representative survey that serum total cholesterol (TC) and non-high-density lipoprotein cholesterol (NHDL-C) levels were lower in patients with current asthma than without current asthma.[7]

It is well established that hypercholesterolemia is associated with enhanced expression of proinflammatory mechanisms leading to increased levels of pro-inflammatory cytokines,[8] cellular adhesion molecules[9] and inflammation-sensitive plasma proteins.[10]

Going by these proinflammatory properties, it has been hypothesized that serum cholesterol may also potentiate eosinophilic inflammation in those with genetic susceptibility for asthma, thereby leading to its increased phenotypic expression.[11] Addressing these gaps in knowledge is essentially important and may lead to newer strategies to tackle two major diseases simultaneously: asthma and dyslipidemia. We aimed to evaluate the relationship between asthma control and various parameters of fasting serum lipid profile.

MATERIAL AND METHODS

This observational prospective cohort study was conducted in large tertiary healthcare centre of North India. Diagnosis of asthma along with its level of control was made according to GINA guidelines 2021.[1] Asthma patients aged more than 18 years, attending our outpatient department were included in the study after counselling and taking proper consent. Patients with respiratory illness other than asthma, having diabetes mellitus, lipid storage disorders, liver disease, psychiatric illness, hypothyroidism, patients taking oral contraceptive pills, lipid-lowering drugs or systemic steroids were excluded from the study. Patients not able to perform spirometry were also excluded. Approval from the ethics committee was obtained on 21/01/2021. *The certificate of approval was belatedly received due to ongoing devastating second wave of covid pandemic.

Total of 150 [Flow Chart 1] patients underwent examination for inclusion in the study along with spirometry, which was done using MIR Spirobank OXI which was calibrated daily. Out of these, 13 patients who could not perform spirometry, 16 patients diagnosed as cases of COPD and 14 patients having diabetes mellitus were excluded from study. After applying inclusion and exclusion criteria for the present study, 107 patients (male: 52, female: 55) of asthma were recruited in study from 1^st February 2021 to 31^st January 2022. The sample size of the study was calculated on basis of a previous study[12] which reported that average prevalence of asthma was 16% in India. Smokers and persons exposed to indoor air pollution were excluded to avoid bias.

Flow Chart 1.

Allocation of Asthma patients in controlled and uncontrolled groups by spirometry after applying exclusion criteria

All recruited asthma patients underwent spirometry (pre- and post-bronchodilator) and were investigated for various fasting lipid profile parameters along with detailed clinical history and physical examination. Fasting serum lipid profile parameters included were TC, triglyceride (TG), LDL, HDL, TC/HDL, TG/HDL, LDL/HDL, very low-density lipoproteins (VLDL) and non-HDL (NHDL). The TC/HDL, LDL/HDL and TG/HDL ratios were calculated by dividing the TC, LDL and TG levels by the HDL levels, respectively.

Among 107 recruited patients, uncontrolled asthma was defined by the presence of one or both criteria, described by GINA 2021,[1] where first criteria included poor symptom control defined by frequent symptoms or reliever use, activity limited by asthma or night awakening due to asthma; and second criteria included frequent exacerbations (≥2/year) requiring oral corticosteroids or serious exacerbation (≥1/year) requiring hospitalization. Patients having spirometry finding of low FEV1 (<60% predicted) and who had high bronchodilator responsiveness were also taken into uncontrolled asthma group. Remaining patients were classified as controlled asthma.

Statistical analysis

We evaluated the difference of various fasting lipid profile parameters in between two groups of asthma patients by using independent t-test. We also evaluated the difference between mean pre- and post-bronchodilator, FEV₁, FVC, FEV₁/FVC in between two groups by using independent t-test.

RESULT

Among 107 patients of asthma, with mean age of 32.97 SD 12.57 years, 69 patients (male: 39, female: 30, mean age: 30.93 SD 11.75 years) were enrolled in controlled asthma group, and 38 patients (male: 13, female: 25, mean age: 36.68 SD 13.31 years) were enrolled in uncontrolled asthma group in accordance with their clinical symptoms and spirometric findings.

Table 1 and Figures 1-3 show the comparisons of mean post-bronchodilator FVC and % pred FVC; mean post-bronchodilator FEV₁ and % pred FEV₁ and mean pre-bronchodilator FEV₁/FVC and % pred FEV₁/FVC in between controlled and uncontrolled groups of asthma patients. In these tables and figures, we see that the mean of post-bronchodilator FVC, % pred FVC; mean of post-bronchodilator FEV₁, % pred FEV₁ and mean of pre-bronchodilator FEV₁/FVC and %pred FEV₁/FVC were expectedly lower in uncontrolled group as compared to controlled asthma group of patients, and all these differences were expectedly statistically significant. (P < 0.05).

Table 1.

Comparisons of mean post-bronchodilator FVC and % pred FVC, mean post-bronchodilator FEV₁ and % pred FEV₁, mean pre-bronchodilator FEV₁/FVC and % pred FEV₁/FVC in between controlled and uncontrolled asthma groups of patients

Spirometric Parameter	Controlled (n=69)		Uncontrolled (n=38)		T	1 P
	Mean	±SD	Mean	±SD
Post-bronchodilator FVC	3.49	0.78	2.83	0.41	4.893	<0.001*
Post-bronchodilator %pred FVC	86.11	10.97	78.08	7.72	3.997	<0.001*
Post-bronchodilator FEV1	2.85	0.59	1.73	0.46	10.063	<0.001*
Post-bronchodilator %pred FEV1	83.38	11.45	56.97	13.18	10.818	<0.001*
Pre-bronchodilator FEV1/FVC	76.99	8.10	49.54	11.43	14.44	<0.001*
Pre-bronchodilator %pred FEV1/FVC	91.55	9.97	59.27	13.06	14.33	<0.001*

*=Significant (P<0.05), ¹=Independent t-test

Figure 1.

Bar chart shows comparative mean post-bronchodilator FVC and % pred FVC in controlled and uncontrolled asthma group of patients

Figure 3.

Bar chart shows comparative mean pre-FEV₁/FVC and % pred FEV₁/FVC in controlled and uncontrolled asthma group of patients

Figure 2.

Bar chart shows comparative mean post-bronchodilator FEV₁ and % pred FEV₁ in controlled and uncontrolled asthma group of patients

Table 2 and Figure 4 show the comparisons of mean lipid profile in between controlled and uncontrolled asthma groups. It was found that despite the levels of different parameters of lipid profile being within the normal standard range in both the groups, mean LDL and TC/HDL ratio were significantly greater in uncontrolled asthma group (mean LDL-73.06 mg/dl SD-30.31, mean TC/HDL- 2.98 SD-1.21) as compared to controlled asthma group (mean LDL-62.14 mg/dl SD-20.73, mean TC/HDL-2.62 SD-0.68). Their P values were 0.030 and 0.047, respectively (p significant at < 0.05). Serum levels of other lipid profile parameters were not significantly different between two groups of study.

Table 2.

Comparisons of mean lipid profile parameters in between controlled and uncontrolled asthma group of patients

Parameter	Controlled (n=69)		Uncontrolled (n=38)		T	1 P
	Mean	±SD	Mean	±SD
TC mg/dl	155.77	35.69	160.49	49.04	-0.57	0.569
TG mg/dl	146.99	78.24	139.96	111.82	0.38	0.704
LDL mg/dl	62.14	20.73	73.06	30.31	-2.20	0.030*
HDL mg/dl	61.53	18.65	59.52	24.7	0.47	0.636
VLDL mg/dl	31.38	15.88	27.9	15.56	1.09	0.277
TC/HDL	2.62	0.68	2.98	1.21	-2.01	0.047*
TG/HDL	2.58	1.58	2.52	1.63	0.19	0.854
LDL/HDL	1.1	0.47	1.37	0.95	-1.97	0.052
NHDL mg/dl	93.36	27.91	100.96	33	-1.26	0.209

*=Significant (P<0.05), ¹=Independent t-test

Figure 4.

Bar chart shows the mean lipid profile in controlled and uncontrolled asthma groups of patients

On doing genderwise comparison of LDL and HDL parameters among patients of controlled and uncontrolled asthma groups, it was found that HDL was higher among females of both groups, while LDL was higher among males of both groups, but this difference was statistically significant only for HDL among females of controlled asthma group (P = 0.000573).

DISCUSSION

Accumulation of immune cells, activation of mast cells and smooth muscle cells, and elevated immunoglobulin E (Ig E) levels are characteristics of asthma and atherosclerosis.[13] When the immune system is active, cytokines are released, which influence fatty acid oxidation and activate hepatic and lipoprotein lipases, leading to dyslipoproteinemia.[14]

In our study, the mean LDL and TC/HDL were significantly greater in uncontrolled as compared to controlled group of asthma patients, but their values were within the normal standard range in both groups. Other lipids such as TC, TG, HDL, VLDL, TG/HDL, LDL/HDL and NHDL were not significantly different between two groups. Previous similar studies have given non-uniform findings. Hence, the findings of present study appear to agree with some while they are not in agreement with others.

Jiayu Peng and Ying Huang[15] found that children with asthma had lower HDL-C levels in comparison with children without asthma while adult asthma patients had higher LDL-C in comparison with adults without asthma. Conversely, they also found that difference in serum levels of LDL-C and HDL-C was not statistically significant in paediatric and adult population, respectively. Another study on paediatric population, done by Vinding et al.[16] looked at the relationship between a child’s lipid profile and their concomitant asthma, lung function, and allergy sensitization. They observed that concomitant asthma, airway blockage and particular airway resistance were all linked to high levels of LDL, while high levels of HDL were linked to lower bronchial hyperresponsiveness, improved specific airway resistance and a decreased likelihood of aeroallergen sensitization.

In a study done by Ko et al.,[17] they looked for comparison between low-risk group and the high-risk group of adult patients, in terms of serum levels for lipid profile parameters and found that high-risk group had considerably greater prevalence rates of asthma. They also found that asthma group patients had significantly higher serum values for TC/HDL-C ratios, LDL-C/HDL-C ratios and non-HDL-C than the non-asthma group (P = 0.05). According to Ramaraju et al.,[5] serum TC in adults is higher among asthmatics than among normal subjects (P < 0.05) and this higher serum cholesterol level in asthmatics is not dependent on age, gender, body mass index (BMI), socio-economic status and serum highly sensitive C-reactive protein (hsCRP) levels. Xinming Su et al.[18] conducted a study to evaluate association of fasting serum lipid profile parameters and asthma among adults. They found that the mean difference for levels of LDL and TC was significantly higher in the asthma group of patients as compared with the control group and no association was observed between asthma and control groups for levels of HDL or TGs.

In another research done by Scichilone et al.,[19] they looked for relationship between different types of LDL and level of asthma control. They found that adults with moderate asthma had lower levels of LDL-1 and LDL-2 than healthy participants. While on the other hand, it was found that asthmatic adults had greater levels of LDL-3 and LDL-4 with the highest pro-inflammatory activity compared to non-asthmatic subjects. Additionally, they also found that level of LDL-3 was inversely correlated with lung function, pointing to LDL-3’s potential role in the inflammatory changes to the airways.

Expert Consensus Statement on Management of Dyslipidemia in Indians[20] stated that Indians develop atherosclerotic cardiovascular disease at a younger age, have malignant disease and high case fatality rates. From this perspective, our finding that HDL is significantly higher among females of controlled asthma group highlights an important aspect, that controlling asthma could also contribute to cardio-protection.

In light of the above previous studies, we can say that there is need for a larger study, having larger sample size, with greater demographic and geographic coverage, to assess the cause-and-effect relationship between level of asthma control and different parameters of fasting serum lipid profile, with particular emphasis on types of serum LDL. It may also clarify whether level of asthma control leads to abnormal lipid profile parameters or vice versa.

CONCLUSION

Fasting serum lipid profile parameters, particularly LDL and TC/HDL were significantly associated with uncontrolled asthma, while other parameters were found to be statistically similar in both groups of asthma patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.