India has at least 60 million to 80 million people with chronic respiratory disease

As we mark World Asthma Day on May 2, Dr Jaideep A Gogtay, Chief Medical Officer, Cipla explains to Viveka Roychowdhury why unlike the rest of the world, 70 per cent of COPD patients in India are non-smokers and why increasing patient compliance, monitoring and awareness are key to tackling chronic respiratory disease. Excerpts from the interaction

Why do we see an  increase in  patients with chronic respiratory diseases (CRD)?

Dr Jaideep A Gogtay

Globally, CRD are believed to affect one billion people. Asthma and chronic obstructive pulmonary disease (COPD) are the two main CRD, while there are several others, like allergic rhinitis for example. Asthma affects just over 300 million, and for the first time, this year, estimates for COPD crossed asthma. (One reason for the increase could be that) we are now able to diagnose more COPD cases in the last five to 10 years and with this better data, COPD incidence is today around 330 million, up from the previous estimate of 210 million. These figures are as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines.

So, while there is a focus on cardiovascular diseases (CVDs), diabetes and cancer, CRD has now also been recognised as a big issue. In fact, COPD is included by the Government of India in the list of non-communicable diseases (NCDs). The challenge with some of the CRD is that in most countries, the ratio of patients diagnosed to undiagnosed is 1:8 or 1:9. So, COPD is vastly under-diagnosed. For example, there was a study in Latin America, which showed that 90 per cent patients were undiagnosed, as diagnosis requires a spirometry or a lung function test.

Where does India stand?

In India, again, the estimates are guesstimates. Asthma patients make up roughly 2-2.5 per cent of the population, which is 30 million people of India’s 1.2 billion total population. An equal number could have COPD. There are some who believe it may be more than 2.3 per cent. Our guesstimate is that there are at least 60 million to 80 million people with CRD in India.

The unique part of COPD in India is that 70 per cent, that’s almost two thirds of the COPD patients are non-smokers, whereas in most Western countries 90 per cent of COPD patients are smokers. The reason is that we have a huge contribution (to COPD figures) from biomass fuel, which women use for cooking in the rural communities. That is why we see the push to move to LPG for cooking. Biomass is also used for heating in the winter, which adds to the COPD burden among non-smokers in India. Of late, we realised that Africa, parts of Latin America too have high numbers of non-smoker COPD patients.

Besides COPD, allergic rhinitis in India is quite high, estimated at around 15 per cent, meaning it is several times more common than asthma. India also has a fairly large population of smokers, estimated around 15-18 per cent. What’s worrying is that while smokers in their 40s are giving up smoking, youngsters seem to be picking it up earlier than before. Also, more young women seem to be picking up (smoking) of late. And beedis do not seem to have lost their appeal. So, we need to track these changes on the smoking front very carefully.

Air pollution too adds to the CRD burden. The Lancet has recently carried an article on the impact of air pollution in various cities and India ranks second in terms of PM2.5, following Bangladesh. This data tells us that air pollution is a big looming problem that will add to our lung health incidence.

We don’t as yet know what is the exact contribution of pollution to CRD but there is an interesting hypothesis put forward around a decade back, that when air pollution, like diesel exhaust, combines with allergies/ allergens like dust mites, cockroach allergies, etc, the lungs amplify the allergic response. So while air pollution may not directly cause asthma, when combined with allergens, the symptoms of asthma may be amplified.

How will these factors impact treatment?

You would see more severe asthma attacks, more difficult patients to deal with, etc. Increasing urbanisation too will add to air pollution levels, with increasing number of vehicles, leading to increased incidence of CRDs. The recent Supreme Court ban on BS III vehicles is a welcome step to reduce vehicular pollution.

Another source of air pollution is dust from roads, construction site activities, industrial pollution. So all these factors are unfortunately very conducive to creating more respiratory problems for us.

Another hypothesis, called the hygiene hypothesis, is that as countries become more prosperous, and the number of infections and exposure to bacteria starts decreasing, the immune system develops a stronger allergic response. Thus, the highest prevalence of asthma is in New Zealand and Australia. We don’t understand everything right now because the immunology (related to CRD) is quite complex.

What are the basic asthma treatment protocols?

Asthma treatment protocols are quite clear. It was very well established in the early 90s that inflammation is the real problem to deal with in asthma. And if you can control the inflammation, you can control the symptoms of bronchospasm, coughs, wheezes, breathlessness attacks, etc. The best drugs for controlling inflammation are corticosteroids. Steroids given by the oral route will always have problems, because they have systemic side effects. But if you give them by the inhaled route, used in the standard therapeutic doses, they have virtually no side effects in most patients. This is supported by data of almost 13-15 years of use of inhaled corticosteroids, even in children aged five to six years.

In many patients, you would need to add a long acting bronchodilator. So this combination is the standard treatment of choice.  There may be 5 per cent patients who may need more medication. But 88-90 per cent patients will do well on this treatment protocol, with no symptoms, no nocturnal attacks and no loss of activities, as long as they follow the doctor’s orders and take their treatment regularly.

What are the major challenges when addressing chronic long term respiratory conditions like asthma, COPD?

Patient compliance is a huge challenge in treatment of asthma. There is a huge drop of around six months of the year, especially during the summer when it’s so hot that the chances of asthma attacks goes down. Most patients stop treatment, for a variety of reasons. Some feel well, the symptoms disappear so they stop taking their medication.

What patients don’t realise is that absence of symptoms does not mean absence of disease. So they stop the treatment, nothing happens for two-three months and then they have an asthma attack when the monsoons start. And then again during the winters, and spring till April. These are the prime times for asthma attacks. So while it’s difficult to get 100 per cent patient compliance in asthma, doctors will be satisfied if their patients stay on their asthma medications for at least nine months of a year, which would mean they are covered for at least 75-80 per cent of the time.

How would low compliance impact the patient in the long run?

If patients do not control their asthma well, then they could face other issues. For instance, normally the bronchi reverse very well but if patient compliance is low, it might reduce and some patients could get fixed airflow obstruction. Similarly, airway remodelling could occur if there is continuous inflammation. This means fundamental changes in the structure of the airways, with the basal membrane of the airway getting thickened. This reduces the flexibility of the airways and such patients may need higher doses of medication. Their lung function may reduce as well. This is a very important reason for making sure patients take their treatment regularly.

How can patient awareness about compliance be increased?

Today every disease condition has a number. For example, a diabetic can track his sugar levels, a hypertensive patient can check his blood pressure, without going to a doctor or a hospital. But until recently, asthma patients did not have such a number to check their status, except to go to a doctor and get a spirometry test done.

Doctors now ask patients to use a peak flow meter to check their lung function, by measuring their peak expiratory flow, which is a good marker, like the glucometer which reads the sugar levels in a blood sample. Now the peak flow meter gives them such a number, in the comfort of their homes, which gives them a reasonably good marker of how they are doing.

What role does device design play in overcoming low patient compliance?

We’ve seen many inhaler designs enter the market. The pressurised metered dose inhaler (pMDI) has been a very popular inhaler, because is it small and allows a patient to be very discreet while taking their medication. All they need to do is step aside and take a puff. But some patients take time to learn or do not have the motor coordination to manage a pMDI so they can use dry powder inhalers (DPIs). Then there are nebulisers, which do not need coordination.

Many patients like the capsules used in DPIs, because psychologically, they are used to medicines coming as capsules, tablets, etc. and feel reassured seeing the powder in the DPI. In a pMDI, the medication is delivered by a spray and the medication per se is not seen. Spacers are also used fairly widely, especially by patients who have poor motor coordination.

What are the latest innovations in inhaler design?

In Cipla, we’ve also been working on breath-activated inhalers. We introduced the autohaler some years ago, which was imported from the UK but the drawback of that was that it did not have a dose counter, which meant that patients did not know how many doses were left. Over the last three years, we have been developing our own breadth-activated device, Synchrobreathe, which is a novel, breath-actuated inhaler (BAI) with a dose counter. No device is ideal because there will always be some patients who will not like it but I think we are moving quite close to that.

Synchrobreathe was launched in South Africa just this January so while it is too early to get patient feedback, physician feedback has been very positive. The whole problem of coordination is solved in a BAI as the patient has to breathe in slowly and deeply and it releases the puff automatically. BAIs are a big step forward as it’s a pMDI, that works like a DPI. There is data to show that if patients like a device, they will use it longer so we believe it will result in better patient compliance.

A very important part of inhaler use is the teaching and training required by a doctor. Doctors don’t have too much time so with a BAI this teaching time is reduced, though not completely eliminated.

Does Cipla have in-house device design facilities or does it partner with or have joint ventures with such companies? Is this where Cipla’s acquisition of a 60 per cent stake in Jay Precision Pharmaceuticals fits in?

We’ve been working with Jay Precision for a long time, who developed all of our devices earlier and have helped with the design of Synchrobreathe as well. Its fascinating what has to come together when it comes to devices. The pharmaceutical scientist, because it is a formulation; engineering because you are dealing with a device, and some understanding of physics. And all this has to be linked with what physicians and patients want, like aesthetics, ergonomics, ease of use. A decade back, patients did not pay much attention to such factors but nowadays, they want sleek, neat looking inhalation devices as well. For instance, when it comes to the choice of cell phones, some would prefer Apple while others would prefer Samsung, yet others would prefer other brands. Similarly, patients too would have preferences for certain inhalation devices.

Good patient feedback is essential to realise what is the preferred device design. For instance, however good a device, in terms of giving a high dose deposition in the lungs for instance, if a patient doesn’t like it, he will not use it and there is not much that can be done to change this preference.

So companies have to keep pace with what the patient wants. Of course, inhalers are more complex, because it involves testing the stability of the formulation, etc so it requires two to three years of various tests before you can come up with a device design, then patient usability studies to see if patients are able to use it.

What are the different formulations intrinsic to respiratory devices currently available in the market?

A typical pMDI contains a suspension or sometimes a solution, containing the drug, along with a surfactant or a lubricant, depending on the drug, to make it homogeneous combined with gas. We use hydrofluoroalkanes (HFA) gas, which is now the standard.

Dry powder formulations consist of the medication and lactose, which are mixed well and micronised to a certain particle size such that the lactose particles are slightly larger than the drug particles. When a patient inhales forcefully and deeply, the two get de-aggregated so that the finer drug particles go down (to reach the lower parts of the lungs) and some of lactose may settle around the throat.

The third type of formulation is respiratory solutions used in devices like nebulisers, which are typically used in hospitals but of late, there is an increasing use of home nebulisation  as the demographic profile changes.

For example, a physician narrated his experience of treating a COPD patient aged 90 years, who was having a problem breathing, and didn’t have the motor coordination to use an inhaler. A home nebuliser allowed the family to take care of the patient’s needs at home. A family member puts the prescribed medication in the nebuliser, fits the nebuliser mask on the patient who then breathes in the medication over the next five minutes. Home nebulisers are thus a relatively new option.

In fact, companies like Philips are now developing hand held, battery operated nebulisers, so that patients can travel with them. Such devices are quite expensive right now but (more affordable) technology will eventually come. Such technologies will become more popular in this part of the world but it also depends on what patients are comfortable with. There is a consensus document coming out on the use of home nebulisers because while it is very popular in the US, Europe and the UK don’t use it much, because they think that a pMDI plus spacer is good enough. But patients may not want this combination. Thus there is obviously a lot of cultural differences between countries. (Patients in) India, China like home nebulisers while the EU, UK do not like them.

What is the way forward?

Increasing patient compliance, monitoring and awareness. Cipla has tried to ensure that all key medications are available through the same device so patients need to learn to use only one type of device, which would increase compliance. Another part is advocating the monitoring (of the disease) by using a peak flow meter to measure the ‘lung power’. Even though they may not be the best tools, they do give some idea of what’s going on in the lungs, of the level of lung function sitting at home. It is also important to create awareness around lung health, for which Cipla started a campaign, Save your Lungs.

And finally, while awareness about heart health and cancer is high, awareness about lung health is very low. And this is very important because of late, there is a lot of work going on about the links between air pollution and diseases beyond CRD. Air pollution has been linked to CVDs, the health of pregnant women and even the foetus as the pollutants can go through the placenta as well.