In the history of medicine, there have been few milestones as significant as the implementation of screening programs to identify diseases like alpha-1 antitrypsin deficiency (AATD) at a stage early enough that they can still be adequately treated. 

The stringent implementation of screening programs worldwide (especially in cervical, breast, and colorectal cancers) represents a tectonic shift in the way the public perceives medicine: that medicine is no longer just about curing an existing pathology, but about preventing it from occurring in the first place. 

In many advanced countries, screening programs are no longer a luxury for the few; instead, they have become a vital part of the public healthcare system. In other words, a physician would be criminally negligent if a breast screening program was not conducted according to stated requirements and the patient ended up with a diagnosis of breast cancer. 


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While many see the implementation of screening programs as a clear example of how medicine is transitioning into a formidable force for public good, a small minority of individuals view this as an unfortunate slide towards an increasingly entitled society; after all, screening programs cannot feasibly be conducted for every disease, and every screening program needs to be paid for, one way or another. However, we will not delve any deeper into discussions about public policy. 

Read more about AATD etiology

The reason that screening programs have such staying power is simple: they save a significant amount of lives every year. In this article, we will look at a screening program conducted in Sweden to identify patients with AATD. 

To Screen or Not to Screen?

Patients with severe AATD have less than 20% of normal plasma circulating levels of AAT. Studies indicate that this cohort of patients tend to develop chronic obstructive pulmonary disease (COPD) up to 2 decades earlier than smokers who do not have the disease. 

The case for a screening program? Hiller and colleagues write in the International Journal of Chronic Obstructive Pulmonary Disease that, “AATD is often clinically underrecognized or misdiagnosed, and the diagnosis is delayed to the point when the pulmonary destruction is already established,” establishing the need for early diagnosis and intervention. 

A literature review of AATD paints a universally negative picture: Patients with AATD experience significantly higher rates of morbidity and mortality compared with the general population; in addition, they suffer from significant lung pathology earlier in life and are susceptible to recurrent exacerbations of their disease. 

Hiller et al conducted a study to investigate the overall health, disease course, and prognosis of patients with severe AATD who have been identified by screening. 

Their study was conducted in Sweden, where a nationwide neonatal screening program for severe AATD was implemented from 1972 until 1974. The purpose of the program was to chart the prevalence of AATD in Sweden; among the 200,000 newborns enrolled in the study, 129 were discovered to have severe AATD. 

The authors of the study farmed data by cross-linkage using the Swedish system of personal identity numbers from the Swedish national patient register, as well as the Swedish national register of causes of death. A total of 1585 individuals with severe AATD were identified. 

Read more about AATD treatment

To validate the severity of AATD, researchers investigated the presence of respiratory disease and liver disease. Laboratory investigations and pulmonary function tests were carried out. Patients were also questioned about their smoking history and occupational exposure to pollutants.

The results of this study elucidate a number of facts that have been reported in other studies previously on individuals with AATD. Those with severe AATD who never smoked had better lung function compared with ever-smokers. In addition, they also had fewer respiratory symptoms and better survival rates. The diagnosis of AATD at an early age before patients started smoking was important to prevent the habit from taking root in the first place. 

Smoking: The Ubiquitous Risk Factor 

Time and again, studies on the clinical course of AATD and other lung diseases have identified cigarette smoking as the common culprit in worsening outcomes and hastening death. 

“Cigarette smoke is estimated to be responsible for approximately 1 in 5 deaths in the United States,” Elicker and colleagues write in Seminars in Ultrasound CT and MRI. “While smoking is best known for its ability to cause emphysema and chronic bronchitis, it is also associated with a variety of other patterns of diffuse lung disease that may also be a source of mortality.” 

The study conducted by Hiller and colleagues above clearly identified smoking as a risk factor for a poorer prognosis among patients with AATD. And smoking is not just associated with lung diseases—it is a significant risk factor for all types of ailments: metabolic, cardiorespiratory, muscular, neurological, and more. 

In Malaysia, where I reside, the government has taken on an extremely bold initiative called the “tobacco generational endgame.” This entails the complete banning of cigarettes for individuals under a certain age, with the hopes of eventually ending smoking once and for all. Granted, there are challenges with this proposal, but it is an initiative that should be applauded. 

Given the abundance of evidence that cigarette smoking worsens real-patient outcomes in severe AATD, among other diseases, do we really need any more convincing to take more forceful action against tobacco use? By combining targeted screening programs with a concerted effort to turn the tide against smoking, we will be investing in a healthier populace. 

Reference

Elicker BM, Kallianos KG, Jones KD, Henry TS. Smoking-related lung diseaseSemin Ultrasound CT MR. 2019;40(3):229-238. doi:10.1053/j.sult.2018.11.010

Hiller AM, Piitulainen E, Tanash H. The clinical course of severe alpha-1-antitrpysin deficiency in patients identified by screeningInt J Chron Obstruct Pulmon Dis. 2022;17:43-52. doi:10.2147/COPD.S340241