Gender-specific differences in comorbidities

Regarding comorbidities, men had higher rates of ischemic heart disease and pulmonary embolism. Women, on the other hand, had higher rates of connective tissue disease, osteoporosis, and depression.

Figure 2: Gender-specific differences in comorbidities

Gender-specific differences in the COPD subgroup of the EARCO registry

When specifically examining patients with alpha-1 antitrypsin deficiency and COPD, differences in risk behavior are initially apparent: Men reported a higher total nicotine consumption, measured in pack-years. Regarding COPD severity, women with COPD were more frequently classified as GOLD grade 1 (mild COPD) and less frequently as GOLD grade 4 (very severe COPD) than men. Nevertheless, women with COPD exhibited a significantly higher symptom burden. Furthermore, women in this subgroup reported at least one exacerbation in the past year more frequently than men.

Independent risk factors for symptom burden and exacerbation

Additional analyses were conducted to investigate potential influencing factors such as smoking status, COPD, and sex on symptom burden or exacerbation. In these studies, female sex emerged as an independent risk factor for increased symptom burden and the occurrence of at least one exacerbation within the past 12 months.

Conclusion

Gender appears to play a role in alpha-1 antitrypsin deficiency in many ways. Due to differences in risk behavior, gender should be given greater consideration in alcohol and tobacco prevention programs. Differences in lung diseases, such as the prevalence of COPD and emphysema in men and bronchiectasis in women, highlight the need for tailored treatment approaches that take gender into account. It is hoped that further research in this area will lead to a better understanding of the relationships and causes of these differences and to the development of gender-adapted treatment strategies.

For people with healthy lungs, a resting saturation level of 92 mg/dL (%) is often considered the lowest acceptable value, and a rapid drop to values below 90 mg/dL (%) is even considered potentially life-threatening. However, in individuals with progressive lung function impairment, adaptation processes occur, which is why a modified perspective may be appropriate: the body can adapt to a lower saturation level to a certain extent.⁴, It is less the absolute value of oxygen saturation that is important, but rather a noticeable drop. However, due to many individual factors, there can be no universally applicable limit value for people with impaired lung function. Generally speaking, one can assume that an oxygen saturation of below 90 % requires treatment and in the long term at a value of below 85 % critical is⁴.

In addition to all these factors that make it difficult to make general statements about the individually "correct" oxygen saturation, measurement errors can also occur due to improper use of pulse oximeters, which usually lead to a reading that is too low. The most common causes for this are:

• Failure to follow the instructions in the user manual
• A device that is too loose or crooked on the finger
• Nail polish, artificial fingernails or nail fungus
• Cold fingers

Despite all these uncertainties, it is advisable to obtain a pulse oximeter for home use, especially for detecting changes in oxygen saturation in people whose lung function is already impaired, such as many people with alphas.

The following advice can be derived from the experiences of our club members:

• Purchase a pulse oximeter for your home medicine cabinet, for example from your local pharmacy or medical supply store; you can also find suitable offers online. Prices range between €20 and €30 (of course, there are also more expensive versions, such as those that store measurement data over time or can even be paired with a smartphone, on which the time course of the measurements can then be displayed – however, users of such sophisticated versions should have a certain affinity for technology and be aware that the added benefit compared to a simpler model is limited).
• Measure your oxygen saturation regularly, e.g. once a week (perhaps together with regular blood pressure measurements), and enter the result along with the measured pulse rate in a table.
• Take measurements calmly and always at approximately the same time of day.
• It is best to start taking measurements after a visit to the doctor, who has confirmed that your current state of health corresponds to your personal normality; this way you can simply take note of the first measurements and do not have to worry immediately if they deviate from what is described as "normal" in relevant magazines or on the internet.
• If you then regularly record and track your oxygen saturation in the following weeks, you will see that the result is subject to certain fluctuations and can vary by +/- 2 %; this is due on the one hand to the measurement accuracy of the devices, but also on the other hand to the fact that oxygen saturation in the body is also subject to certain fluctuations.
• Regular measurements over a period of several weeks will then lay the foundation for your individual, medium- and long-term oxygen saturation.
• If you measure an unusually low value, first check whether the pulse oximeter is correctly positioned on your finger or if other factors could be causing an inaccurate reading; simply repeat the measurement after a rest period of 10 to 15 minutes.
• However, if a significant drop in oxygen saturation from the long-term average is confirmed, you should contact your doctor, especially if you notice other signs that indicate a deterioration in your breathing or general health, or if the measured pulse rate has increased significantly compared to the long-term average.
• If you experience signs of a decline in your well-being, particularly regarding your breathing, it is advisable to measure your oxygen saturation outside of your usual routine and compare it to your long-term average. If you notice a significant drop, you should contact your doctor.
• Monitoring oxygen saturation at shorter intervals is recommended for lung patients if, in addition to chronic symptoms, further acute attacks on the respiratory tract occur, e.g., as part of a cold, a flu-like infection, bronchitis, or a Covid-19 coronavirus infection.

So much for the theory. Figure 1 now shows recordings of the oxygen saturation of a patient with the PI*ZZ profile, whose lungs are damaged by bronchiectasis and emphysema, but whose respiratory pump is still largely intact (for better readability, the manually recorded measurements were transferred to a computer table):

• The recordings were started a few days/weeks after a hospital stay, i.e., at a time of symptom-free „normality“.“
• The level of the measured values is
  • Below what is to be expected for a person with healthy lungs.
  • But significantly higher than what can be expected for those with already severely impaired lung function.
• The fluctuations in the measured values within the range specified above are clearly visible.
• Due to the frequency of measurements with 93 and 94%, these values can be assumed to be long-term averages in this case.
• During the period shown, there is no significant drop in oxygen saturation; this corresponds with the perceptions of the affected individuals, who also did not notice any change in their lung function during the specified period.

The details described are even more clearly visible in the graphical representation of the measured values in Figure 2 than in the table:

• Each blackened cell represents a measurement.
• It is now quite clear that individual measurements can deviate significantly from the mean value, but overall, during an uncomplicated period, the mean oxygen saturation value is stable and, in the present example, lies between 93 and 94%.

Unfortunately, from the perspective of a concise presentation, but fortunately for those affected, the recordings do not show a clear drop in oxygen saturation, but it is clear that – as already mentioned at the beginning – this would have to be significantly larger than 2% from the long-term average in order to be considered a warning sign.

In summary, it can be stated that:

• The pulse oximeter provides patients with lung function problems with an inexpensive device to detect and document a deterioration in lung function.
• Important for its application are measurements over a longer, symptom-free period in order to get a feel for its normal level and the usual fluctuations.
• A pulse oximeter should be in the home medicine cabinet of every Alpha patient with lung problems and should be used regularly.
• Significant drops in measured values should prompt contact with the treating physician, especially if they occur in conjunction with a deterioration of breathing, general well-being, or in the context of another respiratory infection.

For those of you who have now decided to carry out a weekly measurement of your oxygen saturation (and of course also for those who have been doing this for some time), we provide templates of the protocol shown above on our website. download Ready. If you are advised by a doctor to measure your oxygen saturation daily, you can also use this form by applying the scale to the calendar day instead of the calendar week as shown, and using a separate sheet for each month.

Please also note the following: This article contains only general information based on literature references and feedback from our members, and should not be used for self-diagnosis or self-treatment. It cannot replace a visit to a doctor.

Sources:

• https://flexikon.doccheck.com/de/Pulsoximeter
• https://www.cardiopraxis.de/pulsoximetrie-lunge-testen-bei-lungenentzuendung/#:~:text=Unter%20k%C3%B6rperlicher%20Belastung%20bleibt%20die,kein%20Messfehler%20vor%2C%20nicht%20normal.
• https://meinschlaf.de/gesunder-schlaf/sauerstoffsaettigung-im-schlaf-11273/
• https://www.dr-gumpert.de/html/erniedrigte_sauerstoffsaettigung.html

Photo credits: Pulse oximeter Kristini/shutterstock.com; Sleep Gorodenkoff/shutterstock.com

Therapy with AAT

After it became clear that some people with emphysema have an AAT deficiency, attempts were made to supply the body with the missing AAT. The first publication on this topic dates back to 1981 by the American research team led by Ronald Crystal (see Prof. Vogelmeier's presentation). The infusion treatment did indeed increase the AAT level in the blood. This replacement therapy has been used for decades in patients with AAT deficiency-related emphysema, provided the patient meets certain criteria.

Recent small studies offer hope that individuals with the skin disease panniculitis could also benefit from AAT infusions. Small reports are being published on people with AAT deficiency who are being treated with AAT therapy for bronchiectasis, asthma, and other conditions. Since AAT increasingly arises in the context of infections and injuries, other applications for AAT therapy are conceivable. However, animal models must first demonstrate the success of AAT application before human trials can begin.

In addition to classic infusion therapy with AAT, treatment via inhalation is also being tested. Another application method, a cream containing 5-10 % AAT applied to the skin, has only been tested in a small study. This option also requires further investigation.

AAT substitution and lung transplantation

When the lungs are severely damaged, people with AAT deficiency can undergo a lung transplant. After the procedure, AAT replacement therapy is discontinued. At the Hanover Transplant Center, patients who had either received regular AAT treatment before surgery or had not previously received AAT treatment were compared. Post-transplant survival differed significantly between these groups, as those without prior replacement therapy lived longer than those who had received AAT infusions for years: After 10 years, 69 of the patients who had not received replacement therapy before the transplant were still alive, compared to only 26 of the transplant recipients who had received prior replacement therapy. The reasons for this surprising result could not be identified in the study. It is possible that the two patient groups differed in certain characteristics and therefore had different prognoses. For those patients who received this therapy before lung transplantation, it may be important to continue replacement therapy after the transplant.

In animal models, mice treated with AAT after lung transplantation showed fewer rejection reactions. This was demonstrated by researchers in Hanover. Some experts are now considering whether patients should continue to receive AAT replacement therapy after lung transplantation. However, there are no good studies on this topic.

News from experimental research

Normal AAT has a specific spatial structure. In people with type Z AAT, the arrangement of the molecules is altered: several molecules clump together to form large "clumps," known as polymers. Such clumps of type Z AAT are found in many, but not all, liver cells. Polymers are also detected in the blood of all patients with type Z AAT. The question is whether or not this presents a clinical problem.

New studies focused on children with AATD. Some of them develop severe liver disease with cirrhosis as infants and even require a liver transplant. In others, newborns experience a blockage of the liver's bile ducts, a condition known as cholestasis, which later resolves. A third group remains free of liver problems throughout their lives. When researchers examined children in a small study, they found, based on liver biopsies, that polymers were present in the livers of all three groups. Therefore, the presence of polymers in the liver alone is not decisive; other environmental and genetic factors must also be present, such as alterations in lipid metabolism.

Several risk factors are known to contribute to the development of liver cirrhosis in adults with AATD over their lifetime. Alcohol consumption and viral liver infections such as hepatitis and diabetes are particularly significant. Modern methods already make it possible to prevent the formation of Z-AAT polymers. For patients with the Z mutation, one of the researchers' ideas was to inhibit AAT synthesis, thus reducing the production of Z-AAT. In a small phase 2 trial, they administered the substance fazirsiran to 16 people with liver disease. The results showed that the accumulation of Z-AAT in the liver and blood decreased significantly under this treatment. This was also confirmed by histological examination of liver biopsies. However, almost all patients experienced adverse effects such as back or chest pain, diarrhea, dizziness, or shortness of breath. The manufacturer has since launched a larger study to better assess the benefits and risks of fazirsiran.

Z-AAT polymers were studied in the blood of people with AATD and a lung disease. Patients with low polymer concentrations had neither better nor worse lung function scores than those with high polymer levels; therefore, there was no correlation with the extent of lung damage. Researchers are continuing to work on polymers to better understand their functions. Finally, considering that the Vikings spread AATD around the world more than 2,000 years ago, one has to wonder why the disease still occurs today. It is possible that AATD not only causes problems but may also have been beneficial to our ancestors under certain circumstances, such as protecting them from contamination by unprocessed foods.