A review, published in the journal Respirology, sums up recent research on sex differences in a number of common airway diseases, including bronchiectasis. Titled “Increasing awareness of sex differences in airway diseases,” the review was performed by Deepa Raghavan and Raksha Jain from universities of Arkansas Medical Science and Texas Southwestern, respectively, and looked both into cystic fibrosis (CF) and non-CF associated bronchiectasis.
Non-CF associated bronchiectasis suffers from a lack of data on prevalence and mortality. While a study has reported twice the amount of boys as girls in new referrals for bronchiectasis in children, data on adults indicate that women are overrepresented among bronchiectasis patients, specifically among the elderly.
An increasing amount of research has been performed on bronchiectasis associated with non-tuberculosis mycobacterial (NTM) infections. Studies show that up to 30% of bronchiectasis patients suffer NTM infections; however, the type of infectious agents differ between men and women. Men are more often infected with Mycobacterium kansaii, while bronchiectasis in women is often associated with Mycobacterium avium intracellulare. This pattern has led to the term “Lady Windermere’s syndrome” — named after an Oscar Wilde character — describing white, lean, tall, elderly women suffering NTM infection. A prospective study included in the review, indeed, found support for the use of the eponym, with 95% of NTM subjects female, and taller and leaner, than controls.
Rheumatologic diseases, such as rheumatoid arthritis and Sjogren’s disease, was reported to be more common in women, but there are no studies supporting that it carries over to an unequal sex distribution of rheumatologic-associated bronchiectasis. Likewise, the effect of sex hormones on bronchiectasis in post-menopausal women and in women during pregnancy has not been investigated.
In CF-related bronchiectasis, the greater part of the studies showed that women are likely to have worse outcomes and a shorter survival expectancy than men. Women acquire infection with Pseudomonas aeruginosa at an earlier age, and disease progression is more severe. Many studies support the hypothesis that this is likely due to an interaction between estrogen (the primary female sex hormone) and the bacterium, allowing the pathogen to spread more efficiently.
In addition to listing sex differences in bronchiectasis, the review makes a serious effort to offer plausible explanations for the observed differences. While anatomical differences in lung physiology exist, likely accounting for a higher rate of airway disease in male children and — after puberty — in women, anatomical factors cannot alone explain the differences seen.
The influence of hormones has been studied in airway disease, and estrogen has been found to have a number of negative effects on lung function, including a decreased immune response prior to ovulation, when estrogen levels peak. Research on immunological sex differences is, however, equivocal. Studies also find that estrogen drives a shift of the immune response toward a more pro-inflammatory state. These findings need not be contradictory, since inflammation and adaptive immune responses constitute different branches — regulated in part independently — of the immune response.
Studies also showed that men have more immune T-cells than women, a fact linked to male testosterone levels and DHEA, a testosterone precursor, which has been found to decrease allergic inflammation in mice.
Estrogen also reduces the airway epithelium liquid layer, while progesterone reduces the beat of cilia. Taken together, the studies show that female reproductive hormones can reduce the clearance of mucus from the airways, although the authors point out that, so far, the evidence for this is based on experimental studies. Plenty of studies, however, show that women with airway disease often suffer bouts of worsening symptoms during ovulation.
A study also showed that oral contraceptives eased symptoms during ovulation, but authors point out that little is known about the use of hormones in clinical practice for managing airway disease.
Importantly, the review cited studies finding evidence that only 4% of women used drug inhalators correctly — a drastic difference from the 43% of men with correct inhaler use. Female gender was also associated with poorer attendance to pulmonary rehabilitation.
The current review, also presenting data for asthma and chronic obstructive pulmonary disease (COPD), should be an eye-opener for physicians, who by realizing the differences in prevalence, outcomes, and treatment response may optimize care for both men and women.