Bronchial chest tightness, and coughing, particularly at night

Bronchial
asthma is one of the oldest known diseases, but it has only been recognized as
a major public health problem since the mid-1970s.Since then the  prevalence of asthma has been increasing  dramatically, and asthma is now recognized as
a major cause of disability, medical expense, and preventable death.

The
earliest feature  of asthma described was
the labored, rapid breathing typical of asthmatic attacks. The word “asthma” is
derived from the ancient Greek word for “panting.” Initially all breathing
difficulty were considered as asthma only and 
as knowledge about asthma has grown, the features described as
characteristic of asthma have expanded and also breathlessness was
redistributed among cardiac and respiratory diseases.

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Asthma
was first defined in 1959 as “a disease characterized by wide variation over
short periods of time in resistance to flow in the airways of the lung.”1

 National Heart, Lung, and Blood Institute’s (NHLBI’s) 2007
Update on Asthma Pathophysiology and
Treatment Guidelines defines
asthma   as: “Asthma is a chronic inflammatory disorder
of the airways in which many cells and
cellular elements play a role, including mast cells, eosinophils, T
lymphocytes, macrophages, neutrophils, and epithelial cells. In susceptible
individuals, inflammation causes recurrent episodes of wheezing,
breathlessness, chest tightness, and coughing, particularly at night or in the
early morning. These episodes are usually associated with widespread

but variable airflow obstruction that is often reversible
either spontaneously or with treatment. The inflammation also causes an
associated increase in bronchial hyperresponsiveness to a variety of
stimuli.”2

Although many definitions for asthma are there the
well accepted one is GINA definition .

Bronchial
Asthma is a heterogeneous disease usually characterized by chronic airway
inflammation. It is defined by history of respiratory symptoms such as wheeze,
shortness of breath, chest tightness that vary over time and in intensity
together with variable expiratory air flow limitation.3 It is characterized
by bronchial hyper-responsiveness and variable airflow obstruction, that is
often reversible either spontaneously or with treatment.

This
definition involves several components, which are difficult to establish in
routine clinical practice, especially in a resource-limited country like India.
Therefore, Joint ICS/NCCP recommendations regarding guidelines for diagnosis
and management of asthma defines asthma as 
“Asthma is defined as a chronic inflammatory disorder of the airways
which manifests itself as recurrent episodes of wheezing, breathlessness, chest
tightness and cough. It is characterized by bronchial hyper-responsiveness and
variable airflow obstruction, that is often reversible either spontaneously or
with treatment.4

The
global prevalence of asthma, using a definition of clinical asthma or treated
asthma, is estimated to be about 4.5% 5 There has been an increase in
prevalence of asthma over time, similar to other allergic disorders. It is
expected to have additional 100 million asthmatics world wide by 20256

In a
recently conducted World Health Survey, the prevalence of wheezing, clinical
asthma and doctor-diagnosed asthma was 9.63%, 3.3% and 3.16%, respectively in
Indian adults.7 The Indian Study on Epidemiology of Asthma, Respiratory
Symptoms and Chronic Bronchitis (INSEARCH) in adults, which involved 16 centers
across the country in two phases is the largest, prospective multicenter study
on the prevalence of asthma in Indian adults.8 The prevalence of asthma in
adults reported in this study, using a validated International Union against
Tuberculosis and Lung Diseases questionnaire, was 2.05%, with an estimated
burden of 17.23 million.8 Currently, it is reasonable to accept a prevalence
of asthma in India of at least 2% .

Asthma
causes significant Morbidity also .It is the 25th leading cause of
disability adjusted life years (DALYs) lost per year accounting for an
estimated 15 million DALYs lost (about 1% of all lost DALYs).6 This is
similar to other diseases like diabetes mellitus and schizophrenia. Asthma
accounts for 1 in 250 deaths,but most of the asthma deaths are preventable by
adequate treatment.

In
Europe, the estimated direct costs of asthma treatment are about 17.7 billion
Euros every year while the indirect cost due to loss of productivity is about
9.8 billion Euros annually. In India, the estimated cost of asthma treatment
per year for the year 2015 has been calculated at about 139.45 billion Indian
rupees (approximately 2.3 billion US dollars). Interestingly, it has been
deduced that this cost is likely to come down to about 48.5 billion Indian
rupees if all asthmatics receive treatment according to evidence-based
guidelines.9

 

Generally,
most asthma starts from childhood in relation to sensitization to common
inhaled allergens. Many basic and clinical studies suggested that airway
inflammation was a central key to the disease pathophysiology.. The
inflammation is induced by the release of potent chemical mediators from
inflammatory cells and  resulted in
airway remodeling, characterized by thickening of all compartments of the
airway wall .Air way remodelling has 
profound consequences on the mechanics of airway narrowing in asthma and
contribute to the chronicity and progression of the disease.

 

Asthma
is a complex inflammatory disease that involves many inflammatory
cells.Multiple inflammatory effects, including bronchoconstriction, plasma
exudation, mucus hypersecretion and sensory nerve activation has been recognised
in pathogenesis of asthma .

Multiple
inflammatory mediators are involved in asthma, including lipid and peptide
mediators, chemokines, cytokines and growth factors.

This
chronic inflammation may lead to structural changes in the airways, including
subepithelial fibrosis, airway smooth muscle hypertrophy/hyperplasia,
angiogenesis and mucus hyperplasia.

 

 

 

Vitamin
D is a fat soluble vitamin and a secosteroid hormone which is widely recognized
as a modulator of calcium absorption and bone health and further regulates
neuromuscular function cellular differentiation, insulin secretion and blood
pressure10

We now
know that vitamin D receptors (VDRs) are expressed in many cell types  including various immune cells, suggesting
the role of vitamin D on immune system 
These recent findings have increased interest in vitamin D status and
its link to several nonskeletal diseases

Wjst
and Dold were the first scientists to hypothesize a link between vitamin D and
allergic diseases11. The authors suggest that the geographic trend of higher
disease prevalence in more developed countries runs in parallel with vitamin D
exposure. The authors found that higher risk for atopy, allergic rhinitis, and
asthma was associated with increase in vitamin D supplementation for newborns
in order to prevent infantile rickets . A second hypothesis developed later
suggested that vitamin D deficiency may contribute to the recent increase in
allergies in Western countries12

There
is a combination of different factors which determine 25(OH)D serum levels and
vitamin D deficiency like skin pigmentation, low sun exposure, more time spent
indoors, obesity, higher latitudes, and winter season . Other secondary causes
that could affect vitamin D serum levels are diseases including rheumatoid
arthritis, cystic fibrosis, ulcerative colitis, Crohn’s disease, celiac
disease, rickets, and medications 13

Of the
different allergic disorders, perhaps asthma has been the most closely examined
in the context of vitamin D. Although the underlying mechanisms of how vitamin
D modulates the pathogenesis of asthma have not been completely understood, the
available data suggest an association between vitamin D deficiency and asthma.
On the other hand, there is insufficient and weak evidence for an association
between vitamin D status and atopic disease other than asthma

Airway epithelial cells can
hydroxylate 25(OH)D to its active form  
leading to increased differentiation and recruitment of macrophages  enhanced production of cathelicidin and CD14,
and potentiation of host defences against Mycobacterium tuberculosis,  and other bacteria, fungi, and viruses 14

In
addition to promoting appropriate antigen tolerance, vitamin D also modulates
other aspects of allergen-stimulated immune responses. Vitamin D can suppress
production of IgE by human B lymphocytes  in vitro and increase IL-10 production,
promoting a regulatory B-lymphocyte phenotype15 Additionally, vitamin D has
been shown to have the capacity to suppress mast cell activation, reducing
histamine and tumor necrosis factor-alfa release Vitamin D can also promote
mast cell production of anti-inflammatory IL-10 .

 

In the
pathogenesis of non allergic asthma epithelial damage is now understood to
prompt release of cytokines known as alarmins, for
example, IL-25, IL-33, and thymic stromal lymphopoietin, that directly
stimulate multiple cell types, including type
2 innate lymphoid cells (ILC2s) and mast cells. These stimulated ILC2s then
produce Th2-type cytokines, including IL-5,
which in turn promotes eosinophilic inflammation. Vitamin D has been shown to
modulate the epithelial response to stimulation, with a potentially
anti-inflammatory role for this action.16.

Studies
show that vitamin D plays an important role in airway remodelling also.

Airway
smooth muscle cells are involved in airway narrowing as well as in production
of inflammatory mediators involved in asthma. Vitamin D inhibit smooth muscle
cell proliferation as well as inhibit production of inflammatory mediators
there by plays a role in the pathogenesis of asthma.

Vitamin D alters human airway smooth muscle
expression of chemokines and inhibit the expression of a steroid resistant gene
.Vitamin D deficiency has been associated with increased airway hyper
responsiveness ,lower pulmonary function ,worse asthma control and steroid
resistance.17

 

Over
the past few years, several RCTs of vitamin D therapies to improve asthma
control have been completed and their findings published.many of these shows
positive correlation  of poor asthma
control and asthma severity with lower vitamin D levels.