Dynamics of Cough Frequency in Adults Undergoing Treatment for Pulmonary Tuberculosis

Abstract

Background: Cough is the major determinant of tuberculosis transmission. Despite this, there is a paucity of information regarding characteristics of cough frequency throughout the day and in response to tuberculosis therapy. Here we evaluate the circadian cycle of cough, cough frequency risk factors, and the impact of appropriate treatment on cough and bacillary load.

Methods: We prospectively evaluated human immunodeficiency virus-negative adults (n = 64) with a new diagnosis of culture-proven, drug-susceptible pulmonary tuberculosis immediately prior to treatment and repeatedly until treatment day 62. At each time point, participant cough was recorded (n = 670) and analyzed using the Cayetano Cough Monitor. Consecutive coughs at least 2 seconds apart were counted as separate cough episodes. Sputum samples (n = 426) were tested with microscopic-observation drug susceptibility broth culture, and in culture-positive samples (n = 252), the time to culture positivity was used to estimate bacillary load.

Results: The highest cough frequency occurred from 1 pm to 2 pm, and the lowest from 1 am to 2 am (2.4 vs 1.1 cough episodes/hour, respectively). Cough frequency was higher among participants who had higher sputum bacillary load (P < .01). Pretreatment median cough episodes/hour was 2.3 (interquartile range [IQR], 1.2-4.1), which at 14 treatment days decreased to 0.48 (IQR, 0.0-1.4) and at the end of the study decreased to 0.18 (IQR, 0.0-0.59) (both reductions P < .001). By 14 treatment days, the probability of culture conversion was 29% (95% confidence interval, 19%-41%).

Conclusions: Coughs were most frequent during daytime. Two weeks of appropriate treatment significantly reduced cough frequency and resulted in one-third of participants achieving culture conversion. Thus, treatment by 2 weeks considerably diminishes, but does not eliminate, the potential for airborne tuberculosis transmission.

Keywords: airborne transmission; cough; infectiousness; tuberculosis; Peru.

Figure 1.

Flowchart for the Cayetano Cough Monitor Study. Abbreviations: HIV, human immunodeficiency virus; TB, tuberculosis.

Figure 2.

Circadian cycle of cough frequency during treatment for study group. A, Smoothed trends in cough from day –1 to day 7 of treatment. Each day begins at 9 am, as this is the time when recordings began. B, Separate negative binomial generalized estimating equation models fitted for each day following treatment. All recordings, regardless of total length, were included (n = 12108 hours of recording). Random-effects modeling was used to adjust for study participant. Circadian cycles of cough were reflected by sine/cosine terms.

Figure 3.

Kaplan-Meier curves for time to coughing cessation and microbiological conversion in study group. Cough cessation represents the time to the first of 2 consecutive recordings with a cough frequency of ≤0.7 cough events per hour (considered “no cough”); by day 14, the probability of cough cessation was 42% (95% confidence interval [CI], 25%–64%), and by day 60 the probability was 51% (95% CI, 33%–72%). Smear conversion represents the time to the first negative smear with no subsequent positive smear; by day 14, the probability of smear conversion was 26% (95% CI, 17%–39%), and by day 60 the probability was 85% (95% CI, 73%–93%). Microscopic-observation drug susceptibility (MODS) culture conversion represents time to the first negative culture with no subsequent positive culture; by day 14, the probability of MODS culture conversion was 29% (95% CI, 19%–41%), and by day 60 the probability was 94% (95% CI, 85%–98%).