« Unpleasant sensory and emotional experience associated to  real or potential tissue damage or described in terms of such  damage ».

This is a subjective experience that typically accompanies nociception. But pain may also arise in the absence of any stimulus, and thus the proper definition should include the emotional response to actual or potential harm. Nociception, on the other hand, is a purely neurophysiological term that denotes specific activity in nerve pathways.

Physiology

Nociceptive inputs are mediated through a complex system of receptors and pathways. From the effected organ, the nociceptive signal is transmitted through the first order neuron via the dorsal root to a synapse in the spinal cord, crosses the midline to the opposite side of the spinal cord, and reaches the brain’s thalamus through the anterolateral white matter. From the thalamus, the signal is transmitted through the third neuron to the somatosensory cortex.

Pain Function

Pain is a critical component of the body’s defense system which encourages it to disengage from the stimulus associated with pain.

Classification of pain

There exists  different classifications of pain on the basis of :

1.      Duration

- Acute pain : usually of short duration

- Chronic pain : usually persisting  more than  3 to 6 months

2.      Anatomy : following the concerned part of the body

3.      Mechanism : – transient : refers to the response to a painful (noxious) stimulus that does

not produce long-term consequences

-  persistent pain: chronic pain is the response that does produce long-term

consequences

The World Health Organization Pain Ladder

Source : World Health Organization. Analgesic ladder. World Health Organization Tech Rep Ser 1990;804:1-73.

Asthma is a chronic (long-term) lung disease that inflames and narrows the airways. Asthma causes recurring periods of wheezing (a whistling sound when you breathe), chest tightness, shortness of breath, and coughing. The coughing often occurs at night or early in the morning.¹

Asthma is a pathology where acute episodes occur but in reality is a chronic disease.Asthma epidemiology (Source : www.ginasthma.com)

1. According to data from the World Health Organization (WHO) , more than 180,000 people die every year because of asthma.

2. 8% of the Swiss population is suffering of asthma; compared to 2% 25 or 30 years ago.

3. Following the Belgian Allergology Institue “UBC”, the incidence of asthma has grown two times during the last decade in Occidental Europe.

4. In Australia, more than 1 of 16 children < 6 years is affected.

Is it asthma?

The exact cause of asthma isn’t known. Researchers think that a combination of factors (family genes and certain environmental factors) interact to cause asthma to develop, most often early in life.

Anyway, the presence of any of these symptoms should increase the suspicion of asthma:

1. Wheezing – high-pitched whistling sounds when breathing out- especially in children

2. History of any of the following:

• Cough, especially at night
• Recurrent wheeze
• Recurrent difficult breathing
• Recurrent breast tightness

3. Symptoms occur or worsen at night awakening the patient

4. Symptoms occur or worsen in seasonal pattern

5. The patient also has eczema, hay fever, or a family history of asthma or atopic diseases

6. Symptoms occur or worsen in the presence of :

• Animals with fur
• Aerosol chemicals
• Changes in temperature
• Domestic dust mites
• Drugs (aspirin, betablockers)
• Exercise
• Pollen
• Respiratory (viral) infections
• Smoke
• Strong emotional expression

7. Symptoms respond to anti-asthma therapy

8. Patients’colds “go to the chest” or take more than 10 days to clear up

Who is at risk?

Asthma affects people of all ages, but it most often starts in childhood. Young children who have frequent episodes of wheezing with respiratory infections, as well as certain other risk factors, are at the highest risk of developing asthma that continues beyond 6 years of age.

Among children, more boys have asthma than girls. But among adults, more women have the disease than men. It’s not clear whether or how sex and sex hormones play a role in causing asthma.

Most, but not all, people who have asthma have allergies.

How to diagnose?

The measurement of lung function provides an assessment of the severity, reversibility and variability of airflow limitation and helps to confirm the diagnosis of asthma.

Spirometry is the preferred method for measuring airflow limitation and its reversibility to establish a diagnosis of asthma. This test measures how much air you can breathe in and out. It also measures how fast you can blow air out. Your doctor also may give you medicines and then test you again to see whether the results have improved.

If the starting results are lower than normal and improve with the medicine, and if your medical history shows a pattern of asthma symptoms, your diagnosis will likely be asthma.

Your doctor may order other tests if he or she needs more information to make a diagnosis. Other tests may include:

• Allergy testing to find out which allergens affect you, if any.
• A test to measure how sensitive your airways are. This is called a broncho provocation test. Using spirometry, this test repeatedly measures your lung function during physical activity or after you receive increasing doses of cold air or a special chemical to breathe in.
• A test to show whether you have another disease with the same symptoms as asthma, such as reflux disease, vocal cord dysfunction, or sleep apnea.
• A chest x ray or an EKG (electrocardiogram). These tests will help find out whether a foreign object or other disease may be causing your symptoms.

In people with COPD, the air sacs no longer bounce back to their original shape after breathing. And yet, the elastic quality of a healthy lung helps retain its normal structure and helps to move the air quickly in and out.

The airways can also become swollen or thicker than normal, and mucus production might increase. The airways are blocked, or obstructed, making it even harder to get air out of the lungs.

The main causes are air pollutants, principally cigarette.

Symptoms?

This results finally in the various potential symptoms including:

• Constant coughing, sometimes called “smoker’s cough”
• Shortness of breath while doing activities you use to be able to do
• Excess sputum production
• Feeling like you can’t breathe
• Not being able to take a deep breath
• Wheezing

Exacerbations?

COPD may , resulting in an increase in episodes of lung inflammation and more difficulties to breathe. Moreover this is often accompanied by bacterial secondary infections and purulent secretions.

How to diagnose it ?

A diagnosis of COPD should be performed in any patient who has dyspnea, chronic cough and sputum production, and/or a history of exposure to risk factors for the disease, especially cigarette smoking.

Key factors for considering a COPD Diagnosis – consider COPD and perform spirometry if any of these indicators are present in an individual over age 40. These indicators are not diagnostic themselves, but the presence of multiple key indicators increase the probability of a diagnosis of COPD:

• Dyspnea that is : Progressive (worsens over time)

Usually worse with exercise

Persistent (present every day)

Described by the patient as an increased effort to breathe, “heaviness”, “air hunger” or “gasping”

• Chronic cough May be intermittent and may be unproductive

• Chronic sputum production

• History of exposure to key factors:

Tobacco smoke (including popular local preparations)

Occupational dusts and chemicals

Smoke from home cooking and heating fuel

How to treat?
The first action to take into account is a reduction in the exposition to environmental pollutants.

Then treatment should be initiated with first the introduction of short and long acting bronchodilators and possibly glucocorticosteroids in case of more severe disease.

Epidemiology

COPD is the 4^th main cause of deaths worldwide.

Following NHLBI data, more than 12Mio people are diagnosed with it and maybe another 12 Mio people have COPD but ignore it.

Causes may be primary (genetic) or secondary. Diagnosis made is by measuring plasma levels of total cholesterol(TC), TGs, and individual lipoproteins. Treatment includes dietary changes, exercise, and lipid-lowering drugs.

LDL Cholesterol: The Primary Target of Therapy

Following the ATP III -National Cholesterol Education Program guidelines (US) – and research from experimental animals, laboratory investigations, epidemiology, and genetic forms of hypercholesterolemia, high LDL levels are considered to be a major cause of coronary heart disease (CHD) For these reasons, the ATP III guidelines continue to identify elevated LDL cholesterol as the primary target of cholesterol-lowering therapy. As a result, the primary goals of therapy and the cutoff points for initiating treatment are stated in terms of LDL.

For this purpose a lipid profile should be performed every 5 years in people aged 20 years old or older.

The following table shows the classification of LDL cholesterol level adopted by ATP III and also the classification of total and HDL cholesterol.

Risk determinants in addition to LDL-cholesterol include the presence or absence of CHD, other clinical forms of atherosclerotic disease, and major risk factors other than LDL.

Based on these other risk determinants, the ATP III guidelines identify three categories of risk that modify the goals and modalities of LDL-lowering therapy. The following table defines these categories and shows the corresponding LDL-cholesterol goals.

The category of highest risk consists of CHD and CHD risk equivalents. The latter carry a risk for major coronary events equal to that of established CHD, i.e., >20% per 10 years.

CHD risk equivalents comprise:

• Other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease);
• Diabetes;
• Multiple risk factors that confer a 10-year risk for CHD >20%.

Residual Risk

In spite of the standards and guidelines set up, many studies show that in certain cases, statin mono-therapy may not be sufficient to adequately reduce the cardiovascular risk related to dyslipidemia.

Indeed, the DYSIS study showed that =

a) 48% of the patients on statin mono-therapy did not reach the target values in term of LDLc levels

b) 28% continued to have low HDLc levels

c) 38% continued to have high TG levels.

Moreover, the REALIST study showed that low HDLc and high TGlevels, affecting millions of patients in the world, are strongly related to the significant rate of increase in coronary risk, even at patients achieving or exceeding their LDLc reduction goals. The patients whose LDLcare very low (< 70 mg/dl) due to the action of statins, see nevertheless their cardiovascular risk still increased by 60% if their current TG levels remain too high (> 300 mg/dl) or their HDLc levels too low (< 37 mg/dl).

This risk is defined by R3i (The Residual Risk Reduction initiative) like residual cardiovascular risk, whether it is of a micro or macro-vascular nature.

Lipid profile management

All these results lead to the conclusion that the development of specific formulations (such as fixed combination products) allowing management of mixed dyslipidemia would be an added value to public health.

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