INTRODUCTION

Near-fatal asthma (NFA) is an inflammatory disease of the respiratory system in which a conventional therapeutic approach has failed, it is characterized by a refractory asthmatic crisis with a partial pressure of carbon dioxide (PaCO2) greater than 45 mmHg, consciousness level alteration, and mechanical ventilation requirement^1,2. NFA affects 5 out of 100,000 asthma patients per year globally¹. In Peru, there have been no studies at the national level on the clinical-epidemiological characteristics of asthmatic patients who arrive at emergency areas³. However, a study conducted at the Daniel Alcides Carrión National Hospital found that the annual incidence of patients who met the criteria for near-fatal asthma was 4 per 1,000 hospitalized patients diagnosed with asthma⁴.

Several risk factors for death related to asthma have been identified, such as a history of previous intubation, ICU stay, multiple emergency visits during the previous year, abuse of beta-agonist drugs, respiratory tract infections, sensitivity to aeroallergens, age, respiratory tract infections, systemic dependence on glucocorticoids^5-7. Similarly, diabetes mellitus is also a risk factor with great relevance in recent years due to its high incidence worldwide and common comorbidity in asthmatic patients^8,9.

The mechanisms that explain the exacerbation of asthma in diabetic patients are not yet fully elucidated, it is hypothesized that low-grade systemic inflammation and hyperglycemia are key points for their understanding^9-11. Although the coexistence of asthma and diabetes mellitus in the same patient is frequent, there is little information worldwide and none in Peru on near-fatal asthma as a clinical manifestation in diabetic patients, therefore, the aim of this work is to describe the clinical picture in a case of near-fatal asthma as a clinical manifestation in a debut diabetic patient for its recognition in the emergency area and to carry out an adequate therapeutic approach.

DESCRIPTION OF THE CLINICAL CASE

A 40-year-old female patient with incomplete high school, from Moche who works in outpatient commerce, has had asthma for 10 years with irregular treatment, with no family history of the disease. In laboratory tests, he has an arterial blood gas study, he also has type I obesity (BMI: 30) and uncontrolled arterial hypertension. She has history of COVID-19 a year ago and a dust allergy; In addition, her mother was diagnosed with prediabetes approximately 8 years ago.

One week before going to the emergency room and being hospitalized, she presented dyspnea with an insidious onset and a progressive course, generally in the afternoons and at night, which limits her ability to carry out her daily activities and worsens due to exposure to humidity, cold, and the realization of higher efforts. During that week, she presented 3-4 shortness of breath crises a day and went to a medical center near his home to have nebulizations performed.

One day before admission, she suffered crises of acute dyspnea with little effort that did not improve with inhaled salbutamol. In the emergency service, she was admitted with dyspnea accompanied by signs of respiratory distress, poor general condition and an oxygen saturation of 85%, oppressive retrosternal chest pain of severe intensity and generalized cyanosis, disorder of consciousness, snoring in the middle ⅓ and bases of both hemithorax with a predominance of right hemithorax, rhythmic and regular heart sounds. Information on emergency baseline pulmonary function tests could not be obtained.

A few minutes after her emergency stay, she presented a sudden loss of consciousness where a respiratory arrest was identified, for which emergency endotracheal intubation was performed, she was transferred to perform a chest X-ray (Figure 1) and then received support with mechanical ventilation plus sedoanalgesia. A RT-PCR test for SARS-CoV-2 was requested with a negative result and laboratory tests (Table 1). Arterial blood gas analysis (AGA) revealed decompensated respiratory acidosis and hyperglycemia; Furthermore, a high value was obtained in the glycosylated hemoglobin test, for which she was diagnosed with type 2 diabetes mellitus (DM2), decompensated by hyperglycemia. The patient does not present with complications of ketoacidosis or hyperosmolar state, an interconsultation with the ICU was carried out for management in that service; however, it did not have beds available.

Figure 1 Simple anteroposterior projection chest X-ray. Interstitial congestion pattern (Kerley lines), prominence of the pulmonary arterial arch, accentuated bronchovascular pattern, presence of an endotracheal tube with a distal tip projecting close to the carina and a right-access central venous catheter with a distal tip projecting into the superior vena cava 

The next day, the patient remains in support with mechanical ventilation and sedoanalgesia; Physical examination shows absence of breath sounds (silent lung). Subsequently, he received inhalations of bronchodilators by MDI (Metered Dose Inhaler) and corticosteroid therapy. Magnesium sulfate was used as a complement to first-line therapy, to which it did not present a favorable response, so ketamine, norepinephrine, insulin infusion therapy, and antibiotic therapy (ceftriaxone, clindamycin) were indicated due to the suspicion of a bacterial infectious process. over aggregated.

In the subsequent days, during his stay on mechanical ventilator support under the aforementioned conditions, she presented an unfavorable evolution with hemodynamic instability, laboratory tests (Table 2), and high suspicion of pneumonia associated with mechanical ventilation, for which reason the rotation of antibiotics to Carbapenems (Meropenem). After 4 days with the change of antibiotic therapy, she presents a slight ventilatory and hemodynamic improvement, a tracheostomy was performed, after which she was weaned and taken off the mechanical ventilator after 14 days. Later, she is transferred to hospitalization to complete treatment, and from where she is discharged after 20 days.

DISCUSSION

Near-fatal asthma defines a subset of patients with asthma who are at increased risk of death from their disease¹². Studies show that deaths from asthma attacks typically occur in patients with poorly controlled asthma whose condition gradually deteriorates over days or weeks before the fatal or near-fatal episode of asthma occurs¹³. The signs and symptoms that were evidenced in the patient were decreased consciousness level, respiratory distress, cyanosis, auscultatory silence, SatO2 of 89.4% (<90%), PaO2 of 54.4 mmHg (<60 mmHg) and PaCO2 of 49.8 mmHg (>45mmHg), which are consistent with the clinical manifestations of NFA, which could have led to the development of respiratory arrest^1,6,12.

As usual management of NFA, immediate ventilatory support is given to preserve adequate oxygenation, reduce dynamic hyperinflation and reduce probable hypercapnia (confirmed in the AGA); and subsequently administer nebulized B2-agonists, systemic corticosteroids, theophylline, ketamine, or epinephrine, which relieve airflow with reduction of airway obstruction and mucus; depending on the situation^6,14. In this case, the patient was refractory to salbutamol nebulization before admission to the emergency room; After endotracheal intubation and mechanical ventilation, there was no favorable response to magnesium sulfate, so ketamine, norepinephrine, and vasopressors were indicated, described as part of non-conventional therapy⁶.

Several risk factors were identified in this patient, such as low socioeconomic status, irregular treatment of asthma, difficulty in perceiving the severity of her symptoms, and ignorance of the condition of DM2 by the patient and her relatives; which together led to their high risk of death.

Among these factors, DM2 stands out due to its association with worsening asthma control, increasing the chances of exacerbations, complications and hospitalizations^10,11. The hypothesis of its association is based on low-grade systemic inflammation, characterized by high levels of inflammatory markers such as IL-6 and TNF-alpha that favor the differentiation of Th2 cells into Th17 and the production of high levels of IL-17 that are seen in severe asthma; as well as in obese people and those with DM2, conditions present in this patient^10,15,16. Besides, hyperglycemia generates advanced glycation end products that can affect microvascular structures such as the alveolar capillary network in the lung; which reduces lung function and decreases lung capacity¹⁰.

Additionally, research has found a decreased risk of hospitalizations for asthma in diabetic patients who have regular treatment with metformin^16,17, which contributes to the explanation of the almost fatal asthma in this case, since being a debut diabetic patient did not have a treatment before admission.

Despite the precipitating factors for NFA already mentioned and according to the study conducted by Sandrock C, et al.¹⁸, viral infections represented 59% of the patients, with rhinovirus, particularly human rhinovirus-C, being the Most common causative agent detected 5 days prior to asthma exacerbation. Other viruses that cause this complication are also mentioned, such as respiratory syncytial virus (RSV) type A and B, as well as influenza A, which seem to be the most frequent and recurrent threats. In this case, the viral infection by rhinovirus could explain the manifestation of almost fatal asthma in the patient; even more, having diabetes mellitus which generates immunosuppression. However, a severe bacterial infection that is not secondary to a viral infection would be unlikely to cause near-fatal asthma.

The patient did not show symptoms of viral infection days before emergency admission; In addition, no diagnostic tests were performed to rule out the presence of said infection.

In conclusion, the presentation of NFA is rare and has not been reported in Peru as a clinical manifestation in an obese patient with debut DM; for this reason, asthmatic patients with obesity and DM should be monitored due to the susceptibility to developing an NFA.