Secondary Logo

Journal Logo

Original article

The prognostic value of hypophosphatemia in acute exacerbation of chronic obstructive pulmonary disease (COPD)

El-Sayed, Ibrahima,*; El-Dosouky, Mohammedb; Mashhour, Karimb; Fawzy, Suzyb

Author Information
The Egyptian Journal of Critical Care Medicine: August 2017 - Volume 5 - Issue 2 - p 57-60
doi: 10.1016/j.ejccm.2017.04.001
  • Open


1. Introduction

Acute exacerbations of chronic obstructive pulmonary disease (COPD) with decompensated respiratory acidosis lead to repeated hospital admissions and are associated with high mortality, making it the leading cause of disability and morbidity. Although many factors play role in COPD aetiology, it is dominated by smoking. The admission of COPD patients to an intensive care unit is common, as 26%–74% of them need mechanical ventilation (MV) mostly traditional MV [1]. COPD is the fourth leading cause of death worldwide, especially in the aging population, its prevalence and mortality are expected to become the third leading cause of death worldwide by the year 2020 [2].

Phosphorus is an important and an essential electrolyte that plays a significant role in different physiological cellular biochemical processes including the ATP (Adenosine Triphosphate) high energy bonds which have an effect on the muscle contractility, cellular integrity, and other biological functions [3].

Low levels of phosphorus in blood is not uncommon. Lowserum phosphorus levels may be responsible for the state of muscle weakness that further negatively impacts COPD [2]. Also, a low level of phosphorus in the blood increases the exacerbation of COPD severity which may require prolonged ventilation process [1].

In addition, older age, decreased lung function, lower health status, diabetes and previous ICU admission are important risk factors for mortality in COPD patients hospitalized for acute exacerbation which have negative impacts on the patients quality of life, lung function and socioeconomic costs [4].

In this study, we aim to examine and evaluate the effect of low blood phosphorus level on patients admitted with acute exacerbation of COPD regarding need for ventilation, duration of ventilation and outcome.

2. Patients and methods

This cohort study was conducted in the chest department and respiratory ICU at Benha University hospital where we included and examined 50 patients admitted with acute exacerbation of COPD in the period between October 2014 and March 2015.

The included patients ninety percent were males and ten percent were females with mean age 67.54±10.44years. All patients were smokers with mean smoking duration 44.92±12.39years and smoking index was 69.08±24.12pack/year. The included patients were >40years, smokers with chronic obstructive pulmonary disease. They had increased shortness of breath, significant increase in sputum production, or new expectoration of purulent sputum. Their blood gases showed severe respiratory acidosis pH<7.25 and PCO2>60mmHg.

We excluded from our study patients with age <40years, chronic renal failure, diabetic, acute cerebrovascular disease, malignancy, bronchial asthma, and sepsis or any other severe inflammatory illness.

All patients were scheduled for full medical history from the patient (if possible) or his relatives: history of smoking, history of chest symptoms (cough, expectoration, dyspnea, and wheezes), history of previous intubation and or ventilator support. Full clinical examination (general and local). Assessment of exacerbation severity according to GOLD (2014).

2.1. Laboratory investigations

Complete blood picture, kidney function tests (urea, creatinine), liver function tests (AST, ALT), arterial blood gases, random blood sugar, coagulation profile (PT, PTT, INR). Serum electrolytes: Na, K, Ca, Mg and phosphorus on admission.

2.2. Radiological: chest X-ray was done

Each patient signed an informed consent form for blood sampling, data analysis and his acceptance to be included in the study. Approval for our study was obtained from the Ethical Committee of Cairo University Hospital.

SIMV mode was the mode of MV in all patients. Criteria for weaning success or failure: If a patient, after 24h weaning had PO2>70mmHg, PCO2<50mmHg, continued to maintain a respiratory rate of <30times/min, normal cardiovascular function, no irritation, and no paradoxical respiration, the weaning was considered successful; otherwise, as failure.

3. Statistical analysis

The clinical data were recorded on a report form. These data were tabulated and analyzed using the computer program SPSS (Statistical package for social science) version 16 to obtain: Descriptive statistics were calculated for the data in the form of mean and standard deviation (±SD). for quantitative data and frequency and distribution for qualitative data.

In the statistical comparison between the different groups, the significance of difference was tested using one of the following tests: Student's t-test: Used to compare mean of two groups of quantitative data. Inter-group comparison of categorical data was performed by using fisher exact test (FET).

A P value <0.05 was considered statistically significant (S) while >0.05 statistically insignificant P value <0.01 was considered highly significant (HS) in all analyses.

4. Results

This study included 50 patients with male predominance (n=45, 90%) (Male: female ratio 9:1). Their mean age 67±10years. They were admitted with chronic obstructive pulmonary disease (COPD) associated with acute bronchitis in 29 patients (58%), while the rest of the patients (21patients) showed typical pneumonia (42%). According to their outcome, they were classified into group with favorable outcome (n=32) who have been discharged from ICU, and group with unfavorable outcome (n=18) who died.

In comparison of both groups; patients who deceased were significantly older, with higher smoking index and longer ventilation-dependent duration during ICU stay (Table 1). A significant difference in blood gases (except for HCO3) and electrolytes (except for Na) are shown in the same table (Table 1).

Table 1
Table 1:
Shows the demographic features and the clinical characteristics of both groups.

In relation to phosphorus level with 2.5mg as cut off level, patients were classified into hypophosphatemic group and normophoshostaemic group. Table 2 shows the comparison between these 2 groups.

Table 2
Table 2:
Comparing the normophoshostaemic group and hypophosphatemic group among studies patients.

Focusing on both phosphorus and potassium levels, patients with both low levels in potassium (K) and phosphorus (P) had more unfavorable outcome (Table 3).

Table 3
Table 3:
Shows association of hypokalemia and or hypophosphatemia with outcome.

Unfavorable outcome were significant among patients with both low level of phosphorus and potassium with P=0.003 (Table 4).

Table 4
Table 4:
Relation between the level of phosphorus on admission and age, gender, duration of smoking and the need for mechanical ventilation.

5. Discussion

Phosphorus (P) is an important and essential electrolyte that plays a significant role in different physiological cellular biochemical processes including the adenosine triphosphate (ATP) high energy bonds which have an effect on the muscle contractility, cellular integrity and other biological functions [3]. Low serum phosphorus level increases the exacerbation and the severity of chronic obstructive pulmonary disease (COPD) [2]. Hypophosphatemia is common co-morbidity in critically ill patients, often leading to increased mortality, prolonged duration of MV and intensive care unit (ICU) stay [5].

Acute exacerbation of COPD leads to repeated hospital admissions and is associated with high mortality. Respiratory and skeletal muscle weakness is considered a major factor in patients affected with chronic obstructive pulmonary disease (COPD) [5].

The aim of this study is evaluating the impact of normal and low blood phosphorus on admission on patients admitted with acute exacerbation of COPD regarding need for MV, duration of ventilation and outcome.

In our study, 90% of patients were males (male predominance) and 10% females with mean age 67years, all patients were heavy smokers with long smoking duration. These findings coincide with similar studies. Pauwels et al. [6] found in their study that 60% of the admitted patients with exacerbated COPD were males and 40% were females and they were also older in age and with long duration of smoking. Farah et al. [1] found in their study that over 70% of the patients were men and had higher mean age 66.6years. Male predominance in our study may be cultural denial of female smoker revealing.

While previous clinical studies showed that 56.7% of patients with acute exacerbation of chronic pulmonary disease had hypophosphatemia [7], our study results were nearly the same but demonstrated higher prevalence (60%). This may be due to smaller number of studied patients.

According to some of the studies, mortality increases with age [6]. Similarly in another study, the average age of patients who died was 75years [1]. This was consistent with our findings in which older patients (71years) had unfavorable outcome with P: 0.02.

In this study, patients with low phosphorus at admission had higher mortality (unfavorable outcome) than patients with normal blood phosphorus (P: 0.05). Also, Farah et al. 2013 [1] in their study showed similar results in which mortality was higher among patients with low phosphorous compared to those with normal phosphorus with P: 0.009. Concurrently, in similar study, there was significant association between hypophosphatemia and the mortality of patients under ventilator support [5]. Also, Papi et al. [8] found that hypophosphatemia was associated with poor outcome and increased mortality and led to weaning failure.

In this study, the need for mechanical ventilation and longer hospital stay increased in patients with hypophosphatemia more than in patients with normal phosphorus level (P: 0.03 and 0.04 respectively). Similarly, other studies found that the number of days for MV and need of MV were significantly higher in patients with low blood phosphorus level (P<0.001) [1]; and the weaning failure percentage was significantly higher in hypophosphatemic vs the normophoshostaemic groups (P<0.05) [7].

In our study, we found that the combination between hypophosphatemia and hypokalemia had significant unfavorable outcome (P: 0.03). This agreed with the study by Mair et al. [9] in which it found that the combination between hypophosphatemia and hypokalemia increased the need for ventilation and duration of ventilation, also, Fishman et al. [10], found that combination between hypophosphatemia and hypokalemia led to poor outcome and increased mortality due to prolonged ventilation and weaning failure. Also, Farah et al. in 2013 demonstrated that low blood phosphorus and potassium levels could increase mortality in COPD patients in ICU [1].

In our work, we observed a difference in the need for MV and MV period between patients with different blood phosphorus levels, the number of days for MV and need for MV was significantly higher in patients with low phosphorus level. These results were in concordance with the results found in the study done by Farah et al. [1] who found clear association between low blood phosphorus level and course of the disease and need for MV.

In this study, we found that combined hypophosphatemia with multiple electrolyte deficiency increased the need for mechanical ventilation, duration of ventilation and poor outcome. However, in the contrary, Amanzadeh J and Reilly RF [11] found that deficiency of each electrolyte alone (K, Ca, Na) had a bad effect on severity and prognosis of COPD as they caused respiratory muscle weakness and deterioration of conscious level. On the other hand, other studies found in addition to hypophosphatemia, low levels of potassium and magnesium could cause a delay in weaning process [12].

6. Conclusion

Hypophosphatemia may contribute to an increase in the COPD severity, need for mechanical ventilation, duration of ventilation and so increases unfavorable outcome. Therefore, close monitoring and careful adjustment of electrolytes as phosphorus are crucial and may also increase the survival rate of patients with COPD.

7. Limitations

We are unable to correct low level of phosphorus which made us unable to evaluate the effect of normalization of phosphorus level on patient outcome.


[1] Farah R, Khamisy-Farah R, Arraf Z, Jacobson L, Makhoul N. Hypophosphatemia as a prognostic value in acute exacerbation of COPD. Clin Respir J 2013;7:407-415.
[2] Elsammak My, Attia A, Suleman M. Fibroblast growth factor 23 and hypophosphatemia in chronic obstructive pulmonary disease patients. J Med Biochem 2012;31:12-18.
[3] Couillard A, Muir JF, Veal D. COPD recent findings: impact on clinical practice. COPD 2010;7:204-213.
[4] Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management and prevention of chronic obstructive lung disease. Am J Respir Crit Care Med 2014;163:1256-1276.
[5] Shakhawey A, Alawady S, Razek AA. Effect of phosphate level on the outcome of critically ill patients in the intensive care unit. J Am Sci 2015;11:82-88.
[6] Pauwels RA, Buist AS, Calverley PM, Jerkins CR, Hurd SS. Global strategy for diagnosis, management and prevention of chronic obstructive pulmonary disease. NHLBI/WHO global initiative for chronic obstructive lung disease (GOLD) workshop summary. Am J Respir Crit Care Med 2001;163:1256-1276, (8).
[7] Zhao Y, Li Z, Shi Y, Cao G, Meng F, Zhu W, et al. Effect of hypophosphatemia on the withdrawal of mechanical ventilation in patients with acute exacerbations of chronic obstructive pulmonary disease. Biomed Rep 2016;4:413-416, (15).
[8] Papi A, Luppi F, Franco F, Fabbri LM. Pathophysiology of exacerbations of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2006;3:245-251, (9).
[9] Mair G, Miller JJ, Mc Allister D. Computed tomographic emphysema distribution: relationship to clinical features in a cohort of smokers. Eur Respir J 2009;33:536.
[10] Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A. Electrolyte deficiency and mechanical ventilation. N Engl J Med 2009;322:2059-2080.
[11] Amanzadeh J, Reilly Jr RF. Hypophosphatemia: an evidence-based approach to its clinical consequences and management. Nat Clin Pract Nephrol 2006;2:136-148.
[12] Schweickert WD, Hall J. ICU-acquired weakness. Chest 2007;131:1541-1549.

COPD exacerbation; Phosphorus level; Mechanical ventilation; Outcome

© 2017 by Lippincott Williams & Wilkins, Inc.