While investigating obstructive sleep apnea in children, Guilleminault learned in 1977 that snoring children had similar complaints and polysomnography-recorded tachypnea but not sleep apnea. The complaints and tachypnea resolved with adenotonsillectomy. Thereafter, all children with clinical symptoms and history of snoring during sleep were systematically studied with calibrated esophageal pressure monitoring to evaluate for the presence of abnormally increased respiratory effort, independent of the presence or absence of hypopnea and apnea during sleep. These investigations included, by necessity, the associated EEG during sleep.

Guilleminault et al. had well described the obstructive sleep apnea syndrome (OSAS) in children, emphasizing that cognitive dysfunction and abnormal behavior during sleep were important problems in this pediatric age group [1, 2]. However, the description did not fully cover the spectrum of abnormal breathing during sleep. In 1982, Guilleminault and colleagues published a case-series on children with similar clinical presentations to those with pediatric OSAS but with only abnormal flow limitation and abnormally increased effort during sleep, as demonstrated by esophageal manometry (Pes) measurement during sleep, and subsequent response to adenotonsillectomy [3]. Despite emphasizing the “resistive-load” as an important feature when investigating sleep-disordered breathing , nobody followed this lead and the Stanford Sleep Clinic was one of the places where children were systematically studied using Pes to monitor breathing during sleep.

Guilleminault asked Riccardo Stoohs, a young postgraduate fellow from Marburg, Germany, where Guilleminault had been on sabbatical, to investigate things further. Stoohs was enticed to come and perform postgraduate research at Stanford focusing on this abnormal breathing pattern that was now seen not only in children but also in teenagers and young adults. The studies were also performed in adults and for the first time the term “upper-airway resistance” was used and these adult cases were published [4]. These authors explained the reasons for arousal without hypopneas and oxygen de saturation but with significant daytime dysfunction. Unfortunately, these observations were neglected, and the scientific world had just barely accepted the notion of OSAS. The pulmonary specialists became interested in evaluating nocturnal oximetry and breathing during sleep, but investigation of subtle changes in the EEG was neglected.

The Stanford group was inspired by the observations of Toshiaki Shiomi that abnormal efforts during sleep with or without hypopnea or apnea had a clear impact on the intraventricular cardiac septum [5] and decided to investigate further. The same group coined the term “upper-airway resistance syndrome” or “UARS” to describe the condition of abnormal breathing pattern during sleep without necessarily having any oxygen de saturation. The clinical and polysomnographic features were published [6], following which the term UARS was finally accepted by individuals working in the field of sleep medicine.

Even with further evidence of the impact of such abnormal breathing patterns during sleep on cardiovascular variables [7], there was reluctance by sleep specialists to routinely use Pes during polysomnography. The Stanford group tried to see if other variables considered to be “less invasive” could be used, and for the first time, the term “flow limitation” was associated with UARS and “snoring intensity” was evaluated as an alternative [8]. However, the possible usage of “flow limitation” as an alternative to measurement of Pes was only considered when the “nasal cannula pressure transducer” was better defined [9 –11]. In the prior physiological reports, the Stanford group had used a full-face mask with a tightly fitted valve, a pneumotachograph, and Pes for the calculation of flow and tidal volume. This equipment, though well-suited for research purposes, could not be easily transferred to clinical practice. One was left again with measurement of Pes.

In 1999, Housselet and colleagues [9] defined “flow limitation” in adults. Such a measurement provided ease of recognition of UARS, even if it does not always match Pes measurements. The first review on UARS was also published that year [12], and usage of nasal cannula to recognize UARS was emphasized by Epstein et al. [13]. It was clear that, depending on the authors, the term was being used a bit differently [14, 15]. To demonstrate that there was a difference between OSAS and UARS, the Stanford group published diverse investigations looking at the autonomic nervous system responses and brain disturbances [16, 17]. However, the demonstration that OSA could be associated with a local neuropathy was presented by Swedish investigators [18, 19]. Demonstration of progressive destruction of local upper-airway receptors provided evidence that the presence of a different syndrome may occur based on the presence or absence of these receptors which are required to respond quickly and appropriately to a challenge during sleep [20]. When they do not respond, completely different means are necessary to inform the brain to control the problem. This variance may lead to different types of comorbidities.