Effects of the menstrual cycle on lung function variables in women with asthma

Abstract

Rationale: Angiogenesis is a defining pathologic feature of airway remodeling and contributes to asthma severity. Women experience changes in asthma control over the menstrual cycle, a time when vessels routinely form and regress under the control of angiogenic factors. One vital function modulated over the menstrual cycle in healthy women is gas transfer, and this has been related to angiogenesis and cyclic expansion of the pulmonary vascular bed.

Objectives: We hypothesized that changes in gas transfer and the pulmonary vascular bed occur in women with asthma over the menstrual cycle and are associated with worsening airflow obstruction.

Methods: Twenty-three women, 13 with asthma and 10 healthy control subjects, were evaluated over the menstrual cycle with weekly measures of spirometry, gas transfer, nitric oxide, hemoglobin, factors affecting hemoglobin binding affinity, and proangiogenic factors.

Measurements and main results: Airflow and lung diffusing capacity varied over the menstrual cycle with peak levels during menses that subsequently declined to nadir in early luteal phase. In contrast to healthy women, changes in lung diffusing capacity (DL(CO)) were associated with changes in membrane diffusing capacity and DL(CO) was not related to proangiogenic factors. DL(CO) did not differ between the two groups, although methemoglobin and carboxyhemoglobin were higher in women with asthma than in healthy women.

Conclusions: Women with asthma experience cyclic changes in airflow as well as gas transfer and membrane diffusing capacity supportive of a hormonal effect on lung function.

Figure 1.

Airflow and fraction of nitric oxide (NO) in the exhaled breath measures over the menstrual cycle in women with asthma and healthy women. Airflow changes significantly in healthy women and women with asthma over the menstrual cycle. Closed circles represent women with asthma and open circles represent healthy control subjects. Asterisks represent significant changes from Week 1 (all P < 0.05).

Figure 2.

Lung diffusing capacity for carbon monoxide (Dl_CO) and its components, the alveolar capillary membrane diffusing capacity (Dm), and lung capillary blood volume (Vc), and circulating CD34⁺CD133⁺ progenitor cells over the menstrual cycle in women with asthma and healthy women. Circulating levels of CD34⁺CD133⁺ progenitor cells also change over time in women with asthma similar to healthy women. Closed circles represent women with asthma and open circles represent healthy control subjects. Asterisks represent significant changes from Week 1 (all P < 0.05).

Figure 3.

Relation of CD34⁺CD133⁺ progenitor cells to airflow (%FEV₁ and FEV₁/FVC) in women with asthma.

Figure 4.

Airflow as determined by %FEV₁ is related to the lung diffusing capacity (Dl_CO).