**4. The characteristics of warning signs and prodromal symptoms of AECOPD**

The characteristics of warning signs and prodromal symptoms among AECOPD patients is important to prevent and manage exacerbations. It is different recognition in COPD patients. AECOPD state is the event that was showed in 'visible' and 'invisible' symptoms [11]. Visible symptoms were presented in struggles to breathe until cannot breathe and invisible symptoms were presented in really bad, massive anxiety, panic attack, and all things worse like liked being trapped in a life-threatening situation that is differently in each person.

The specific factors influencing recognition of exacerbations were heterogeneity of exacerbations and habituation to symptoms. They made the patients know the beginning of exacerbation symptoms, included increased fatigue, increased respiratory symptoms (coughing, sputum production, and breathlessness), specific pain and fever [12]. As supported by Chin [13], he stated about exacerbation experiences and the awareness of prodromal symptoms in the days preceding an exacerbation that (1) patients had an unique, individual pattern of exacerbation symptoms that recurred with each exacerbation event, (2) two very distinct types of exacerbation presentations: sudden onset and gradual onset, a change from the participant's typical day-today COPD symptom variation, exacerbation occurred from a few hours to 2 weeks, it changes individually, (3) treatment for their exacerbation based on the severity of their symptoms, with participants experiencing sudden, severe dyspnea presenting earliest for treatment, and (4) the severity of symptoms in these individuals precipitated a sense of urgency regarding their situation.

Moreover, COPD Foundation and WebMD reported 17 warning signs and symptoms of AECOPD that COPD patients able to know or recognize how much a COPD flare-up will affect them to make decision in how quickly they can be treated for prevention and treatment of an exacerbation before it becomes too severe, until unable to manage those signs and symptoms. They were consisted of (1) cough more than base line, (2) wheezing more than base line, (3) gurgling or rattle breathing, (4) more dyspnea, (5) more shallow breathing or rapid breathing, (6) produce more mucous than base line, (7) change color in the mucus from clear to green/yellow/ tan/bloody, (8) excessive sleepy, (9) confusion, (10) swollen ankles and/or feet, (11) loss of appetite, (12) blue tinge to lips or fingertips, (13) yellow or gray skin, (14) difficult to talk, (15) headaches first thing in the morning, (16) abdominal pain, and (17) chest pain [14]. WebMD [15] stated that there are 9 early warning signs of AECOPD, included (1) noisy breathing, (2) irregular breathing, (3) worsening cough, (4) change color in nails or/and skin, (5) problem sleeping and eating, (6) unable to talk, (7) early-morning headaches, (8) swollen ankles or legs or belly pain, and (9) fever. Moreover, if COPD patients have 4 symptoms; (1) chest pain, (2) blue lips or fingers, (3) confuse or get very easily upset, and (4) dyspnea and unable to talk together, they have to visit the doctor and receive the treatment soon because they can start to become severe suddenly. National Institutes of Health (NIH) [16] divided the

warning signs of AECOPD quite differently among COPD Foundation and WebMD reported, it divided the warning signs into two groups, included common early signs and other possible signs. The common early signs consisted of three warning signs; (1) trouble catching patients' breathe, (2) noisy and wheezing sounds, and (3) cough, sometimes has more mucus than normal day or change color in the mucus. The other possible signs consisted of 10 warning signs; (1) unable to take deep breathing, (2) difficult to sleep, (3) morning headache, (4) abdominal pain, (5) anxiety, (6) difficult to talk, (7) swollen ankles or legs, (8) gray or pale skin, (9) blue or purple lips or nail tips, and (10) unable to talk in full sentences.

According to above reporters, awareness of warning signs and prodromal symptoms depended on the perception of each patient who has experienced exacerbation individually. Most warning signs and prodromal symptoms, such as increasing of fatigue, cough, sputum production and breathlessness through hours into 2–7 days [3].

Chatreewatanakul et al. [3] studied about exacerbation experiences among COPD Thai patients. In Thailand, COPD is the fourth most common cause of death and the number of deaths due to COPD is increasing every year. In 2012–2014, there were 1421, 1597, and 1619 COPD-related deaths [17]. The mortality of COPD patients increased from 7.7 deaths per one hundred thousand people in 2013 to 11.4 deaths per one hundred thousand people in 2017. Furthermore, there were 8598 deaths/fiscal year and exacerbation is the most cause of death [18], which is the same cause of death as the world's population that a slow decline of the disease trajectory in COPD, punctuated by dramatic exacerbations that often end in unexpected death or unpredictable death [19]. They found that the characteristics of warning signs and prodromal symptoms could be described in three categories: 1) early signs and symptoms, 2) signs and symptoms that make the patients worse, and 3) time of occurrence.

#### **4.1 Early signs and symptoms**

COPD patients recognizes warning signs and prodromal symptoms according to their individual experiences. Early signs and symptoms of AECOPD consisted of two types; 1) frequent early signs and symptoms that are coming before cannot breathe and 2) other early possible signs and symptoms that are coming before cannot breathe.

#### *4.1.1 Frequent early signs and symptoms that are coming before cannot breathe*

Most COPD patients have three early signs and symptoms that frequent early occurs before the beginning of AECOPD, included: (1) cough, (2) more dyspnea, and (3) cannot exhale. Cough is the most of signs and symptoms that frequent early occurs before the beginning of AECOPD. More dyspnea and cannot exhale are the second and third respectively.

Since the mechanism of an exacerbation in COPD patients makes cough, more dyspnea, and cannot exhale are related each other. AECOPD is often stimulated by dyspnea which related to respiratory tract infection by bacteria or virus infection, environmental pollution, or unknown factors. During exacerbation state, increasing of hyperinflation and gas trapping, reduce expiratory flow, consequently dyspnea increase [5, 6, 20]. When the participants are ill with respiratory bacteria or viral infection, they will have a cough. This sign will induce dyspnea and result in unable to exhale continuously. Finally, this will induce AECOPD occurring.
