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The lines of treatment

Studies don't dispense with the use of corticoid inhalants, except in very mild cases

For a long time now asthma has been treated with bronchial dilators administered through nebulizers during the crisis of the lack of air. Nevertheless, when the inflammatory character of the illness became clear, treatment then went on to include corticoid inhalants (anti-inflammatory chemicals). The regular inhalation of corticoids almost always allows for the control of the inflammation and the avoidance of a crisis with few side effects, since the product almost always remains restricted to the lungs. Though over the last few years there have been many studies developed in order to obtain new drugs against asthma, not one, for now, can be compared to the efficiency of the inhaling corticoids.

Avoidable deaths
A study by Dr. Martins’ interdisciplinary group at the Medical School-USP shows that in São Paulo more than 80% of the deaths from asthma could have been avoided. Marisa Dohlnikoff analyzed thirty fatal cases and verified that at least twenty five patients had been taking totally inadequate medicine – only bronchial dilators and no other anti-inflammatory. Also, in twenty eight cases they had been in crisis for more than twenty four hours before they had arrived at hospital.

The post-mortem showed that the chronic inflammation had produced irreversible alterations in the pulmonary tissue, with the accumulation of collagen fibers that had favored the loss of elasticity as well as obstructing the alveoli. “With the exception of patients who have less than one crisis per week, it is essential to treat the asthma with anti-inflammatory substances in order to avoid these irreversible alterations. Only bronchial dilators are not enough”, underlines Martins.

Because of this, Dr. Martins is looking to contribute to perfecting the anti-inflammatory therapies. For example, a survey by Ana Lúcia Cabral has shown that the medication cannot be prescribed based only on the intensity of the symptoms as usually happens. This is because, in many cases, there is not a direct correlation between the gravity of the inflammation and/or that of the pulmonary obstruction and the level of discomfort felt – above all the lack of air.

In order to arrive at this conclusion, Ana Lúcia studied eighty four asthmatic children from 5 to 14 years of age. During three months the children daily noted and measured their symptoms using a special apparatus that measured the maximum velocity with which air was expelled from their lungs, a good indicator of the level of inflammation. The study showed that, in the majority of the patients, there is no direct relationship between the intensity of the symptoms and the objective situation of the lungs.

Distorted perception
Some children who were sufferers of serious asthma had, in 45% of the cases, a perception that underestimated the problem, while the others, only with slight asthma, had an exaggerated sense 100% of the time. These results motivated the group to develop efficient, non-invasive methods, for measuring the inflammatory level. “It is important to evaluate the intensity of the inflammation, in order to administer the most efficient medication in the correct dosage”, stresses Martins. She also reminds that psychological disturbances such as stress and depression, that accentuate the symptoms of asthma, can be aggravated by some of these bronchial dilators currently in use. On the other hand, research by the group has proven the influence of nervous alterations in starting off an asthmatic crisis.

Yes to Exercises
The studies by Dr. Martins’ team also showed that, contrary to what many people believe, physical exercise – when done at the appropriate intensity – is essential to guarantee the quality of life of asthmatic sufferers. To this end, at the Exercise Laboratory, mounted through financing by FAPESP, and coordinated by the physiotherapist Celso Fernandes Carvalho, a group of asthmatic adults was submitted to intense physical efforts that brought on asthma crises.

The comparison between the symptoms and the level of pulmonary obstruction showed, however, that in a good number of the patients the moment of the greatest lack of air didn’t coincide with the greatest pulmonary obstruction. “This shows that the greatest discomfort is very often caused by the lack of physical fitness and not only by the asthma”, explains Martins.

Specific drugs
The researchers emphasized that no new drug or new treatment against asthma, immunotherapeutic or not, has had in human beings an efficiency so ample as the inhaling corticoids. The problem with these drugs, nevertheless, continues to be with their side effects. In spite of being rare when applied via inhalation, the effects can include hoarseness, throat infection, aggravation of osteoporosis, and in the case of children, even a slowing down in growth. A new therapeutic treatment is with the anti-leukotrienes, but they only work well on asthmatic sufferers for whom exercise or aspirin start off their crisis, a group that only represents 10% of the total patients.

Another family of drugs, in the final phase of testing, in that of the anti-immunoglobulin E (IgE), which inhibits the production of this antibody that is related to asthma. The expectation, nonetheless, is that the anti-IgE will also only be effective for a sub-group of asthmatic sufferers. “Perhaps this will be the future: specific treatments for each type of asthma”, speculates Martins, highlighting, nonetheless, that in the near future patients could gain a lot from the application of knowledge already available about the illness and with the perfecting of the use of corticoids. “Unfortunately, a sizeable number of medical doctors still treat asthma only with bronchial dilators”, she says, recalling a survey on children sent to the Darcy Vargas Hospital. “Not one was re-admitted once they began to be treated with adequate medication.”

Homeopathy and genetics
In spite of her defense of the corticoids, Martins admits that other treatments, such as homeopathy, can lead to good results. “There are few studies about this, but the majority of the patients have told her that they have managed satisfactory results through homeopathic treatment.” The search for drugs and treatments is only one of the research lines on asthma in the world. Another, in plain expansion, is the investigation of the genetic mechanisms that turn some people predisposed to developing the illness and others not.

Though still distant from practical applications, these studies could be revolutionizing the treatment of asthma. Researchers in Europe, the United States and Canada are working on this line of research, in which one of the most expressive names is the pneumologist from the state of Rio Grande of Sul, Dr. Noé Zamel, who has been working for decades at the University of Toronto.The high mark in Brazilian asthma studies, concentrates on environmental factors that make the illness increase throughout the world. There are important research groups in this area at the Federal Universities of São Paulo (Charles Naspitz and Dirceu Solé) and of Rio de Janeiro (José Roberto Lapa e Silva), and at the Catholic Pontificate University (PUC) of Porto Alegre.

“What has become clear is that asthma is a syndrome provoked by innumerable causes and that its treatment should include not only drugs, but the education of patients and their families about how to identify and avoid allergic substances and about the importance of moderate exercise”, evaluated Martins. Exactly with these objectives in mind, associations of asthmatic sufferers are on the increase throughout the world (one has been recently created in Brazil) and the World Health Organization has established the Global Initiative for Asthma (Gina), which maintains a site on the Internet.

The Project
Evaluation of the Inflammation of Air Passages in Asthma: Development of Experimental Models and Clinical Studies (nº 98/00190-2); Modality Thematic project; Coordinator Dr. Milton de Arruda Martins – Medical Faculty of USP; Investment R$ 295,488.28 and US$ 123,789.25