ABSTRACT
Introduction:
Acute respiratory distress syndrome (ARDS) is a life-threatening condition. ARDS carries a high mortality, and few effective therapeutic modalities exist to combat this condition. The etiology of ARDS can be expected to be different in India due to the higher incidence of tropical infectious diseases. However, not many studies have been done in India on ARDS. This study was planned to evaluate the epidemiological profile of patients with ARDS in a tertiary care hospital in the sub-Himalayan region of Himachal Pradesh, India.
Methodology:
It was a hospital based prospective study which was conducted in the department of medicine of Dr. Rajendra Prasad Government Medical College and Hospital, Kangra (at Tanda), a tertiary care referral hospital. Duration of study was 1 year, viz, January 2020 to January 2021. All patients above the age >18 who presented with ARDS satisfying the given definition presenting in Emergency of DRPGMCH Kangra were included in the study.
Results:
A total of 75 patients with ARDS admitted from emergency in various wards of the hospital after triaging. Our study observed that the cause of ARDS did not have a significant association with severity of ARDS (P = .209). We observed that among 30 patients with severe ARDS, 24 patients had involvement of all four quadrants and six patients had involvement of three quadrants. Involvement of all quadrants was significantly associated with a severe ARDS (P < .001). Requirement of inotropes was not significantly associated with the severity of ARDS (P = .669). We observed that the patients with severe ARDS had significantly lower levels of albumin in comparison to moderate and mild ARDS (P = .021). We observed that the patients with severe ARDS had significantly higher levels of PCT in comparison to moderate and mild ARDS (P < .0001).
Conclusion:
ARDS carries a very high mortality, irrespective of the cause and the risk factors that were associated with poor prognosis included older age, female sex, presentation during rainy seasons, high SOFA and APACHE II scores at the time of presentation, requirement of MV, requirement of early inotropes, high PCT levels, low albumin levels, and the severity of ARDS at presentation.
Keywords: Acute respiratory distress syndrome, ionotropes, mechanical ventilation, tropical infection
Introduction
Acute respiratory distress syndrome (ARDS) is a critical condition that primary care physicians should recognize as it often develops in the context of severe illness or injury. ARDS is characterized by acute onset, poor oxygenation, and pulmonary infiltrates.[1] At the microscopic level, it involves capillary endothelial injury and diffuse alveolar damage. Early identification and referral are crucial for improving patient outcomes.
Globally, the incidence of ARDS varies. In Europe, the incidence is around 0.48 cases per intensive care unit (ICU) bed over a duration of more than 4 weeks. Comparable rates in other regions include North America (0.46), South America (0.31), Asia (0.27), Africa (0.32), and Oceania (0.57).
For primary care physicians, understanding the diagnostic criteria for ARDS is vital. The condition typically begins within seven days of an inciting event and is marked by bilateral lung infiltrates and severe, progressive hypoxemia in the absence of cardiogenic pulmonary edema. Diagnosis involves measuring the arterial oxygen tension (PaO2) relative to the fraction of inspired oxygen (FiO2), with a PaO2/FiO2 ratio below 300 confirming ARDS. The updated Berlin definition, introduced in 2012, standardizes these criteria.
ARDS progresses through three phases:
Exudative phase: Characterized by alveolar-capillary damage, inflammation, and fluid leakage into the lungs.
Proliferative phase: Represents partial recovery, with evidence of healing and improved lung function.
Fibrotic phase: Indicates the end stage, which may result in long-term scarring and impaired lung function.
While ARDS carries a high mortality rate, primary care physicians play a critical role in recognizing early risk factors and facilitating timely intervention.[2] These risk factors include chronic alcohol abuse, hypoproteinemia, advanced age, severe illness or trauma (e.g., high ISS or APACHE scores), multiple blood transfusions, and smoking.
The global epidemiology of ARDS has been extensively studied, but research in India remains limited.[3,4] The higher prevalence of tropical infectious diseases in India may influence the etiology and presentation of ARDS.[5,6] For primary care physicians in India, this highlights the need for vigilance, especially when managing patients with respiratory distress and tropical infections.
To address the knowledge gap, a study was initiated to evaluate the epidemiological profile of ARDS patients in a tertiary care hospital in the sub-Himalayan region of Himachal Pradesh, India. Insights from such studies can help primary care physicians better understand the condition’s regional patterns and improve early diagnosis and management
Methodology
Aims and objectives
To study the epidemiological, etiological, and laboratory profile of patients above the age of 18 years presenting with ARDS in emergency of Dr. RPGMC, Tanda Kangra, Himachal Pradesh, India.
It was a hospital-based prospective study that was conducted in the department of medicine of Dr. Rajendra Prasad Government Medical College and Hospital, Kangra (at Tanda), a tertiary care referral hospital. The hospital provides specialized services to the needs of the population residing in the geographical region of Kangra, Hamirpur, Una, Bilaspur, and the lower parts of Mandi and Chamba districts of Himachal Pradesh. This hospital caters to more than 50% of the population of this state. Permission from the institutional ethical committee was taken. The duration of the study was 1 year, viz, January 2020 to January 2021.
Inclusion criteria
All patients above the age >18 who presented with ARDS satisfying the given definition presenting in Emergency of DRPGMCH Kangra were included in the study.
Diagnosis of ARDS
A patient studied was included using the Berlin Definition for ARDS which defines:
Onset: Within 1 week of clinical insult known to result from ARDS.
Mild: Hypoxemia defined by PaO2/FiO2 ≤300 with PEEP or CPAP ≥5 cm H2O.
Moderate: Hypoxemia defined byPaO2/FiO2 ≤200 with PEEP or CPAP ≥5 cm H2O
Severe: Hypoxemia defined byPaO2/FiO2 ≤100 with PEEP or CPAP ≥5 cm H2O
Chest X-ray: Bilateral opacities not fully explained by effusions, atelectasis, or nodules.
Noncardiac etiology: Respiratory failure not fully explained by cardiogenic pulmonary edema. Exclude hydrostatic edema if no clinical risk factor is present.
Exclusion criteria
Those patients who did not consent to be part of this study were excluded.
Those patients who did not satisfy the criteria for ARDS according to Berlin’s criteria.
The patient’s age is less than 18.
Patients with pre-existing lung diseases were excluded.
Procedure for data collection
A detailed case history was recorded on a structured proforma. Basic data on age, sex, education, occupation, smoking and tobacco-chewing status, alcohol consumption, diet, and physical activity were collected from all the subjects. All the subjects were interviewed regarding history of hypertension, diabetes, chronic lung diseases, heart disease, chronic renal failure, cirrhosis of liver and any other comorbid conditions. All patients were thoroughly examined both for general and systemic manifestations of various organ involvement to rule out involvement of cardiac etiology or other volume overload states which may present with similar features of ARDS. All anthropometric measurements, such as waist circumference and body mass index, were recorded using standardized procedures. Systemic examination of cardiovascular, nervous, respiratory, abdomen, and musculoskeletal system was performed. All baseline investigations along with investigations to identify the inciting agents were done and systematically recorded in a structured proforma. All baseline investigations along with investigations to identify the inciting agents were done and systematically recorded in a structured proforma. Acute Physiology and Chronic Health Evaluation (APACHE II) score, SOFA (sequential organ failure assessment score), and Glasgow coma scale (GCS) were also calculated.
Statistical analysis
The data was entered into a Microsoft Excel sheet. The data were presented as frequency, percentages, or mean ± SD whereas applicable. Pearson correlation was used to find a correlation between continuous variables. Statistical analysis was performed using Epi Info version 3.4.3.
Results
The present study aimed to determine the profile of patients with acute respiratory distress syndrome [Table 1]. A total of 75 patients with ARDS were admitted from emergency in various wards of the hospital after triaging [Figure 1].
Table 1.
Baseline characteristics
| Variable | Value (n) |
|---|---|
| Mean age (years) | 50.5±16.8 |
| Sex (male:female) | 43:32 |
| Alcohol consumption | 31 |
| Smoking | 27 |
| BMI (kg/m2) | |
| <18.5 | 2 |
| 18.5−24.9 | 36 |
| 25.0−29.9 | 33 |
| >30 | 4 |
| Comorbidities | |
| Hypertension | 16 |
| T-2 DM | 9 |
| Dyslipidemia | 3 |
| Days from onset of illness | 6.13±4.17 |
Figure 1.
Symptom presentation histogram
In the present study, sputum/ET aspirate cultures were positive in 20% of patients and urine cultures were positive in 4% of patients, while 2.7% of patients had positive blood cultures [Table 2].
Table 2.
Microorganism in sputum (n=15)
| Frequency | Percent | |
|---|---|---|
| Pseudomonas | 6 | 40.0 |
| E. coli | 3 | 20.0 |
| Klebsiella | 3 | 20.0 |
| Polymicrobial | 3 | 20.0 |
| Citrobacter | 2 | 13.3 |
| Acinetobacter | 1 | 6.7 |
| MRSA | 1 | 6.7 |
| MSSA | 1 | 6.7 |
| S. pneumoniae | 1 | 6.7 |
In the present study, 56% of the patients died while the remaining 44% of patients survived. Among the survivors, 25 patients were discharged, six patients were referred, and two patients left against medical advice (LAMA).
We also observed that season of presentation did not have any significant association with the severity of ARDS (P = .563) [Figure 2]. Our study observed that the cause of ARDS did not have a significant association with severity of ARDS (P = .209). We observed that among 30 patients with severe ARDS, 24 patients had involvement of all four quadrants, and six patients had involvement of three quadrants [Figure 3]. Involvement of all quadrants was significantly associated with a severe ARDS (P < .001). Requirement of inotropes was not significantly associated with the severity of ARDS (P = .669). We observed that the patients with severe ARDS had significantly lower levels of albumin in comparison to moderate and mild ARDS (P = .021). We observed that the patients with severe ARDS had significantly higher levels of PCT in comparison to moderate and mild ARDS (P < .0001). Our study observed no significant difference between mean age of the patients with survivors and nonsurvivors (51.3 ± 13.6 vs. 55.9 ± 15.1; P = .186). We observed that 32% of survivors and 61.5% of nonsurvivors were females. Female sex was significantly associated with mortality of the patients (P = .016). 47% of the survivors and 15.4% of nonsurvivors were smokers. Nonsmokers had significantly higher mortality (P = .007). In our study, presentation during rainy season was significantly associated with higher mortality in the patients with ARDS (P < .0001). Our study observed that mean SOFA score was significantly higher in nonsurvivors in comparison to survivors (8.31 ± 3.9 vs. 5.4 ± 3.7; P = .003). Mean APACHE II score was significantly higher in nonsurvivors in comparison to survivors (16.7 ± 6.4 vs. 11.5 ± 7.1; P = .003). Our study observed that 69.2% of the nonsurvivors had indirect cause of ARDS, while 38.8% of survivors had indirect causes [Table 3]. Of the 16 patients with unknown cause of ARDS, four (25%) patients died. Proportion of patients with indirect causes was higher among nonsurvivors with a significant P value in comparison to survivors (P = .019). Our study observed that 79.2% of the patients who required mechanical ventilation did not survive [Table 4]. Requirement of mechanical ventilation was significantly associated with mortality (P < .0001) [Figure 4].
Figure 2.
Severity of ARDS
Figure 3.
CXR findings
Table 3.
Main etiology of ARDS
| Etiology | Frequency | Percent |
|---|---|---|
| Direct causes | 22 | 29.3 |
| Bacterial Pneumonia | 12 | 16.0 |
| COVID 19 | 5 | 6.7 |
| Viral pneumonia with superimposed bacterial pneumonia | 3 | 4.0 |
| Aspiration pneumonia | 1 | 1.3 |
| VAP | 1 | 1.3 |
| Indirect causes | 37 | 49.3 |
| Scrub typhus | 18 | 24.0 |
| Pancreatitis | 6 | 8.0 |
| Leptospirosis | 5 | 6.7 |
| Urosepsis | 3 | 4.0 |
| Puerperal sepsis | 2 | 2.7 |
| 2,4 Diethyl poisoning | 1 | 1.3 |
| Acute calculous cholecystitis | 1 | 1.3 |
| Acute cholangitis | 1 | 1.3 |
| Not known | 16 | 21.3 |
| Total | 75 | |
Table 4.
Association between survivor and nonsurvivor with demographic and other parameters
| Survivors | Nonsurvivors | P | |
|---|---|---|---|
| Age | 51.3±13.6 | 55.9±15.1 | 0.186 |
| Sex | |||
| Male | 13 | 10 | 0.016 |
| Female | 16 | 6 | |
| Smoking | 23 | 4 | 0.007 |
| SOFA Score | 8.31±3.9 | 5.4±3.7 | 0.003 |
| APACHE II Score | 16.7±6.4 | 11.5±7.1 | 0.003 |
| Requirement of mechanical ventilation | 19 | 5 | <.0001 |
| Inotropes | 15 | 7 | 0.49 |
| Rainy | 17 | 13 | <.0001 |
| Summer | 2 | 8 | |
| Winters | 30 | 5 |
Figure 4.
Requirement of mechanical ventilation
68% of the patients who required inotropes did not survive. Although, requirement of inotropes was not significantly associated with mortality (P = 0.49). Mean PCT levels among nonsurvivors were significantly higher in comparison to those patients who were discharged (P < .0001). Mean albumin levels among nonsurvivors were significantly lower in comparison to those patients who were discharged (P = .013). Our study observed among nonsurvivors, 46% patients each had moderate and severe ARDS. Among the patients who were discharged, 53% patients had moderate, and 36.7% had severe ARDS. We observed that mortality was significantly higher in the patients with moderate and severe disease (P = .005) [Table 5].
Table 5.
Association between severity of ARDS and outcome
| Mild | Moderate | Severe | P | |
|---|---|---|---|---|
| Death | 2 | 12 | 12 | 0.005 |
| Discharged | 5 | 26 | 18 | |
| Referred | 3 | 3 | 0 | |
| Total | 7 | 38 | 30 | |
Discussion
The incidence of ARDS is significantly associated with age. Studies have reported a 16-fold higher incidence in patients over 70 years compared to those under 30 years, likely due to the higher prevalence of comorbidities in older patients. In our study, 57% of ARDS patients were male. Gender differences have been implicated in the management and outcomes of ARDS. Sex hormones influence inflammatory and immune responses, yet human studies show mixed results. Some research suggests no gender difference in infection or trauma outcomes, but two studies found increased mortality in critically ill patients with elevated endogenous estrogens, regardless of sex. In our study, female gender was significantly associated with higher mortality (P < .05), whereas an Indian study reported higher male mortality at 57%.[7,8] During the rainy season, higher mortality rates were observed, likely due to the increased incidence of scrub typhus, which is endemic in Himachal Pradesh. Smoking was significantly associated with ARDS severity. Smoking affects neutrophil function, immunity, and alveolar macrophages, increasing the risk of ARDS. Calfee et al. reported that both smoking history and biomarkers correlate with a higher ARDS risk in patients with nonpulmonary sepsis.[8] This highlights the need for targeted tobacco regulations. Patients requiring inotropic support at admission had significantly higher mortality (P < .05), likely due to more severe disease at presentation.
Patients requiring mechanical ventilation exhibited higher mortality rates. Gupta et al. reported 90-day mortality of 56% and 55% in patients with ARDS at the onset and after mechanical ventilation, respectively, compared to 46% in patients without ARDS (P < .01).[9]
In our study, 29.3% of patients had a direct cause of ARDS, with bacterial pneumonia (n = 12) and COVID-19 (n = 5) being the most common. Bangoechea and Bamford suggested that SARS-CoV-2 enhances bacterial colonization, leading to tissue destruction, systemic dissemination, and increased sepsis risk.[10,11,12,13]
Procalcitonin (PCT) levels were significantly associated with ARDS severity and mortality. PCT is a recognized marker for bacterial sepsis, and its elevation may indicate complications, including pulmonary ones. Cheng and Chen identified PCT as a warning signal for postoperative ARDS, while Hui et al. linked PCT and IL-6 levels to ARDS severity and multiorgan dysfunction syndrome (MODS).[14,15]
Our study found a strong correlation between higher SOFA (Sequential Organ Failure Assessment) scores and mortality (P < .05). Patients with a SOFA score ≤6 had better outcomes. Vincent et al. demonstrated that initial and peak SOFA scores predict outcomes, with scores >11 indicating >80% mortality risk.[15]
Similarly, higher APACHE (Acute Physiology and Chronic Health Evaluation) scores were associated with increased severity and mortality. Saleh et al. recently reported that APACHE II was a significant predictor of mortality (P < .041).[16] Lower serum albumin levels were linked to severe disease and higher mortality in our study, underscoring the importance of nutritional status in ARDS prognosis. For primary care physicians, recognizing these risk factors and understanding the common etiologies is crucial for early diagnosis and management, particularly in regions where tropical infections like scrub typhus are prevalent. Timely referral and intervention can help mitigate the high mortality risk associated with ARDS.
Conclusion
This study highlights that ARDS has a high mortality rate, regardless of its cause. Poor prognostic factors include older age, female sex, rainy season onset, high SOFA and APACHE II scores, need for mechanical ventilation or early inotropes, elevated PCT levels, low albumin levels, and severe ARDS at presentation.
·Risk factors for severe disease were older age, smoking, elevated PCT levels, and low albumin levels. Scrub typhus was the most common cause of ARDS, followed by bacterial pneumonia and pancreatitis.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
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