Chronic Obstructive Pulmonary Disease (COPD) is the fourth cause of mortality
in the United States, which has infected more than 16 million people in the
US. The disease is ranked as the sixth most prevalent cause of death in the
world, which probably will be the third in 2020 (Reilly Jr
et al., 2008). Patients with COPD occupy 10% of hospital beds each
year and nearly 500 thousand COPD patients are discharged from hospitals yearly
(Roman and Briggham, 2007).
COPD refers to a spectrum of diseases characterized by airflow limitation that
is not fully reversible and includes emphysema, chronic bronchitis, small airways
diseases, etc. New studies have reported new factors in the incidence and exacerbation
of the disease, one of which is serum 25-hydroxy vitamin D (25-OHD) level (Janssens
et al., 2009, 2010). These studies have found
various results including a direct relationship between serum 25-OHD level and
pulmonary infections, chronic infections, obstructive pulmonary diseases, autoimmune
diseases, cancers, etc. Also, some studies have linked this vitamin with symptoms
such as weakness of the skeletal muscles, cardiovascular diseases and cancers
(Janssens et al., 2010; Ginde
et al., 2009).
In relation to the role of vitamin D in the immune system, it has been stated
that vitamin D can regulate the activities of T-cells and products of interleukin-10
(IL-10). In addition, vitamin D reduces the inflammatory response in the airways
and reduces the unpleasant effects of the risk factors of COPD and oxidative
stresses (Janseens et al., 2010; Wright,
2005; Ginde et al., 2009; Hughes
and Norton, 2009; Janssens, 2009). Moreover, studies
have shown that the matrix metalloproteinase enzyme plays a role in the destruction
of the lung tissues in patients with COPD and vitamin D can inhibit the production
of this enzyme. Additionally, individuals without a history of cigarette smoking
but with vitamin D deficiency have a pulmonary function which is 35% lower than
the function in those with a history of cigarette smoking but with an ideal
serum vitamin D level. The ideal level of vitamin D for adults is at least 75
n mol L-1. Serum vitamin D level decreases in the late middle age.
In healthy individuals, around 20-30 mL year-1 of the FEV1 amount
is reduced and this reduction reaches 50-100 mL year-1 in patients
with COPD. The reductions in these two cases may be related with each other
Black and Scragg (2005).
In some studies, a statistically significant relationship has been found between serum 25-hydroxy vitamin D (25-OHD) level of lower than 20 ng mL-1 and the severity of COPD in the third and four stages of the disease according to the Gold Criterion. Therefore, the present study investigated the relationship between FEV1 amount and serum 25-hydroxy vitamin D (25-OHD) level in COPD patients.
MATERIALS AND METHODS
This cross-sectional study included all the COPD patients having the inclusion criteria who presented to Shohada Ashayer Hospital of Lorestan University of Medical Sciences (west of Iran) from April 2011 to July 2011. A convenience sampling method was applied and the following formulae were used to calculate the sample size:
Considering r = 0.28, the sample size was calculated to be 170 patients.
The inclusion criteria of the study included having the age of over 18 years old, being infected with COPD, undergoing spirometry under standard instructions, being monitored by one physician, not using oral corticosteroids and not having a history of vitamin D supplements.
The COPD patients admitted to the Special Clinic of Shohada Ashayer Hospital of Lorestan University of Medical Sciences were selected based on the inclusion criteria of the study. After informed consents were obtained from the patients, spirometry was performed in each patient. Spirometry was performed in all the patients considering the conditions of not having a heavy meal 3-4 h before the spirometry, not being in the acute phase of COPD, having stable hemodynamic conditions, being in the sitting position 15 min prior to the spirometry and not consuming bronchodilator sprays during the last 12 h.
Then the patients were referred to a laboratory which cooperated in measuring serum 25-hydroxy vitamin D (25-OHD) level for the study. The data were gathered using the patients evaluation forms and the tables of spirometry and 25-OHD values. The patients evaluation form consisted of two parts of demographic data and health and disease history with an emphasis on recent diseases of the respiratory tract, consumption of antibiotics and inhaled corticosteroids and so on. The collected data were then analyzed by the SPSS software and statistical analyses were performed.
The present study included 170 patients admitted to the Special Clinic of Shohada Ashayer Hospital of Khorramabad (west of Iran). The data of 145 patients were finally evaluated and analyzed statistically based on the two major variables of the study including serum 25-hydroxy vitamin D level and FEV1 amount. Moreover, the values of p<0.05, 0.05≤p<0.08 and p≥0.08 were considered as significant, fairly significant and insignificant.
The results showed that the means of 25-OHD and FEV1 of the subjects were 64.02±43.14 and 61.72±16.02 respectively. Most of the patients (63.5%) had normal 25-OHD level. Most of them (66.7%) were in the moderate phase (II) and only 5% were in the severe phase (IV) of the disease.
The t-test results showed no significant difference between males and females in terms of 25-OHD level (p = 0.083). Moreover, there was a fairly significant difference between FEV1 means of males and females (p = 0.061). In addition, there were no significant differences between means of 25-OHD (p = 0.230) and FEV1 (p = 0.293) in cigarette smoking and non-smoking groups. Also, no statistically significant differences were found between means of 25-OHD (p = 0.917) and FEV1 (p = 0.837) in the group with a history of smoking with hookah and the one without a history of smoking with hookah. A statistically significant difference was found between means of 25-OHD level (p = 0.024) in the group with a history of bread baking and the one without a history of bread baking while no significant difference was found between these two groups in terms of FEV1 means (p = 0.110). The t-test results also revealed no significant differences in terms of 25-OHD (p = 0.181) and FEV1 (p = 0.712) means between the group with a history of respiratory infection in the last month and the one with no respiratory infection history.
The results of independent t-tests showed a statistically significant difference between the group with a history of antibiotics consumption in the last month and the group with no history of antibiotics consumption (p = 0.034). Moreover, no statistically significant difference was found between these two groups in terms of FEV1 means (p = 0.891) (Table 1).
The results of independent t-tests also showed no statistically significant differences between the group with a history of inhaled corticosteroids consumption and the group with no history of inhaled corticosteroids consumption in terms of 25-OHD level (p = 0.1) and FEV1 level (p = 0.303). In addition, the results of one-way ANOVA did not show significant differences between different age groups in terms of 25-OHD level (p = 0.286) while significant differences were found between different age groups in terms of FEV1 means (p = 0.000) (Table 2).
The positive Pearson correlation coefficient between age and 25-OHD levels showed a direct linear relationship, but it was not statistically significant (p = 0.183). However, the negative Pearson correlation coefficient between age and FEV1 values showed an inverse linear relationship that was strongly statistically significant (p = 0.000) (Table 3).
The non-linear regression showed that the relationship between age and vitamin
D levels could be shown approximately as a third-degree curve (p = 0.078).
|| FEV1 and 25-OHD values in terms of a history of antibiotics
consumption in the last month
|| FEV1 and 25-OHD values in terms of a history of inhaled corticosteroids
|| Graph 1: FEVI in terms of age
Also, the linear regression showed that the relationship between age and FEV1
values could be shown as a linear plot with a negative slope (p = 0.000) (Fig.
The positive Pearson correlation coefficient showed a direct and linear relationship between 25-OHD and FEV1, which was statistically significant (p = 0.009) (Table 4).
Concerning the major aim of the study, a direct linear relationship was found
between serum 25-OHD levels and FEV1 values in the patients, which was statistically
significant (p = 0.009). Therefore, the first hypothesis of the study, stating
a significant relationship between the means of serum 25-OHD levels and FEV1
values, was approved. A direct relationship was found between serum 25-OHD level
and FEV1 value (COPD severity) in a study carried out on 414 smoking patients
aged over 50 by Janssens et al. (2009) that investigated
the relationship between serum 25-OHD level and COPD severity (p<0.0001;
r = 0.28) and this result was consistent with the result in our study.
In another study by Franco et al. (2009), the
relationship between vitamin D and FEV1 was reported as a significant linear
relationship. The serum vitamin D level was used as a marker to determine the
severity of COPD and this result was consistent with our study as well. In a
study by Black and Scragg (2005), a strong significant
correlation was found between serum 25-OHD level and FEV1 values (p<0.0001),
being consistent with the result in our study.
In relation to the aim of the study regarding the determination of a history of the upper and lower respiratory infection in the last month, the majority of the patients (52.8%) had no history of respiratory infection. Therefore, no significant relationship was found regarding the relationship between the upper respiratory infection and serum 25-OHD level (p = 0.181).
The study conducted in 2009 by Ginde et al. (2009)
reported that in the patients with low levels of vitamin D, the prevalence of
influenza and respiratory infections increases. Additionally, the Third National
Health and Nutrition Study in the US carried out on 19 thousand adult patients
with COPD reported the normal range of vitamin D to be = 30 ng mL-1.
Moreover, the prevalence of the upper and lower respiratory tract infections
increased by 40% in patients with vitamin D levels lower than 10 ng mL-1
(Hu and Cassamo, 2000). But in the present, study the
majority of the patients (63.5%) had normal levels of vitamin D and only few
patients had serum vitamin D levels lower than 10 ng mL-1. One the
other hand, since the sampling was performed in a season of the year when the
prevalence of viral, bacterial and other respiratory infections is lower, no
significant relationship was found between these two variables in our study.
The following results were obtained regarding other effective variables in the study which were evaluated and analyzed.
A statistically significant relationship was not found between sex and serum
25-OHD levels (p = 0.083) and different results may be achieved in other studies
with larger sample sizes due to the proximity of the P-value in our study to
the level of significance. In the present study, there was a fairly significant
relationship between gender and the mean FEV1 (p = 0.061). Moreover, in Mannino
(2003) study carried out , a significant relationship was found between
sex and FEV1 level, so that, the level of FEV1 was lower in males due to more
cigarette smoking which was consistent with our result.
In this study, a significant inverse linear relationship was found between
age and FEV1 (p = 0.000), so that, the relationship between age and FEV1 value
can be presented as a linear plot with a negative slope. Moreover, a linear
relationship was revealed between age and levels of 25-OHD, which was not statistically
significant (p = 0.183) and the relationship between age and vitamin D based
on non-linear regression was presented approximately as a third-degree curve
(p = 0.078). Black and Scragg (2005) did not report
a significant relationship between age and 25-OHD levels (p = 0.12).
The present study showed no statistically significant relationship between
smoking and mean of 25-OHD level (p = 0.23) while Black
and Scragg (2005) showed that serum 25-OHD level was lower in smokers who
smoked more than 20 cigarettes daily in comparison to non-smokers and a relative
relationship was found between serum 25-OHD and FEV1 levels in smokers and non-smokers
(p = 0.059).
In addition, in the present study, no statistically significant relationships were found between FEV1 values and other variables such as smoking, use of hookah, history of baking bread and consumption of inhaled corticosteroids and antibiotics.
Black and Scragg (2005) reported in 2005 that although
smoking, age, sex and race, etc. are important factors in determining the lung
function, they do not justify all the differences among people. Regarding the
variable of smoking, Agarwal et al. (2010) reported
that although COPD is more common in smokers, not all smokers will suffer from
COPD and a decrease in FEV1 and only 15% of smokers developed COPD while 20%
of COPD patients did not mention a history of tobacco consumption.
After considering the effects of variables such as age, sex, smoking, hookah smoking and antibiotics and inhaled corticosteroids consumption, etc. that can affect the lung function (FEV1) and serum 25-OHD level, the study showed that there is a significant linear relationship between serum 25-hydroxy vitamin D level and values of FEV1 in patients with chronic obstructive pulmonary disease (p = 0.009). In other words, our results showed that COPD patients without inhaled corticosteroids consumption have lower vitamin D level that is closely related with COPD severity. It means that serum vitamin D level can be used as a marker to determine the severity of COPD. Thus, it seems that determining the level of vitamins, particularly vitamin D, can be helpful in applying complementary medicine in the treatment of chronic obstructive pulmonary disease.